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Prepared by
John E. Fogarty International Center

for

Advanced Study in the

Health Sciences

U.S. DEPARTMENT OF

HEALTH AND HUMAN SERVICES

Public Health Service

National Institutes of Health

NIH PubUcation No. 83-62
July 1983

Foreword

On behalf of the National Institutes of Health
(NIH), the John E. Fogarty International Center
for Advanced Study in the Health Sciences (FIC)
is pleased to present this I'tth Annual Report of
International Activities , covering the fiscal year
1982. Edited by the FIC, but based upon reports
by each of the Bureaus, Institutes, and Divisions
(bid's) of the NIH, this report provides an over-
view of international activities for the period.
These activities are essential to the furtherance
of the NIH mission and fall within the purview of
one or more of the BID's.

The international programs of the NIH are
specifically authorized under the International
Health Research Act of 1960 (P.L. 86-610) to
"advance the status of the health sciences in the
United States and thereby the health of the
American People through cooperative endeavors
with other countries in health research, research
planning, and research training. . . . "The bene-
fits of NIH international programs, however,
extend far beyond our borders. Cooperative
relationships that the BID's have established
through their intramural and extramural pro-
grams enable foreign biomedical and behavioral
research scientists to collaborate with their U.S.
counterparts to discover better means for
treatment, control, and~ultimately~prevention
of disease worldwide.

In 1968, the Fogarty International Center was
established as the focal point for the interna-
tional work of the NIH. Although the number and
kinds of international programs differ from
Institute to Institute, the FIC is the only NIH
component with an explicit international mis-
sion, which includes NIH-wide coordination of
activities relevant to this mission in addition to
the conduct of specific international programs of
its own.

The international activities of the NIH serve
many scientific purposes, dictated by the spe-
cific objectives of the intramural and extramural
programs of the categorical Institutes and the
support and service Divisions. Implementation of
these activities must in turn be responsive to and
consistent with national and international pol-
icies. FIC coordinative functions link the NIH
with other components of the Department of
Health and Human Services, the Department of
State, the Immigration and Naturalization

Service of the Department of Justice, the U.S.
Information Agency, foreign embassies in this
country, science attaches, and multilateral
organizations such as the World Health Organi-
zation (WHO) and the Pan American Health
Organization (PAHO). At the same time, inter-
national activities from year to year reflect
changes in the health scene as advances are
made and new challenges emerge. The NIH also
recognizes the important needs of developing
nations and has fostered contacts that are
described in this report.

In its coordinative functions, the FIC has
relied upon the cooperation of the BID's in
providing the information for this report. To-
gether we hope that the material is selected and
presented in a way that is useful to a wide
audience—including officials and the scientific
community here and abroad—and illustrates the
many ways international programs and activities
contribute to biomedical and behavioral research
and national health not only for the United
States but also for the world at large. In assem-
bling the overall report, we have made certain
editorial modifications to the reports submitted
by the individual BID's to achieve a consistent
format. Because of size limitations, some dele-
tions have been necessary. However, care has
been taken not to alter the scientific content.

The first chapter of the report presents high-
lights of international activities that are de-
scribed in greater detail in the individual BID
chapters. In Chapter II, "Highlights of Recent
Scientific Advances," we have chosen to empha-
size two types of international research activ-
ities: international biomedical collaboration
(between U.S. and foreign scientists) and re-
search in which foreign locations or population
groups are important to the furtherance of
scientific knowledge. Chapter III, prepared by
the Office of the Director, FIC, describes
activities and accomplishments of the programs
conducted by the Center, as well as its coor-
dinative and administrative functions. Subse-
quent chapters discuss international programs
and accomplishments of the individual BID's.
Tables and figures summarizing NIH interna-
tional activities in FY 1982 are appended.

In contrast to the previous report, there is no
separate chapter on activities with individual

111

countries. Rather, we have provided two indexes: of interest and use to a variety of audiences, and

one that refers to descriptions of activities with we welcome comments that will enable us to

individual countries and one that permits loca- achieve more fully this objective for future

tion of material on specific diseases, conditions, reports,
and research areas.

Within the limitations of a single report it is Mark S. Beaubien, M.D.

difficult to summarize the complex nature of Acting Director

NIH international activities and their contribu- Fogarty International Center and

tions to betterment of health in the United Acting Associate Director for

States and abroad. Nevertheless, in this docu- International Research

ment we have attempted to provide information National Institutes of Health

Contents

page

Foreword iii

I Overview of International Activities 1

II Highlights of Recent Scientific Advances 3

Components of the National Institutes of Health 9

III John E. Fogarty International Center for Advanced Study in the Health Sciences 11

IV National Cancer Institute 28

V National Heart, Lung, and Blood Institute k5

VI National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases 61

VII National Library of Medicine 66

VIII National Institute on Aging , 70

IX National Institute of Allergy and Infectious Diseases 73

X National Institute of Child Health and Human Development 87

XI National Institute of Dental Research 90

XII National Institute of Environmental Health Sciences 93

XIII National Eye Institute 99

XIV National Institute of General Medical Sciences 103

XV National Institute of Neurological and Communicative Disorders and Stroke 104

XVI Warren G. Magnuson Clinical Center 107

XVII Division of Computer Research and Technology 108

XVIII Division of Research Resources 110

XIX Division of Research Services 112

Appendix 115

Index by Country 128

Index by Research Area 129

Tables and Figures

Table page

3-1. Scholars-in-Residence, 1982 1^

^-5. Countries/areas of origin of ICRETT awardees and their destinations, 1976-82 35

4-2. The exchange of scientists under NCI's bilateral agreements programs 36

4-3. Patient data, by cancer site and collaborating institute, entered into the ICPDES system . . 38

4-4. International cancer research technology transfer 40

4-5. Countries/areas of origin of ICRETT awardees and their destinations, 1976-82 41

4-6. The NCI-PAHO collaborative cancer treatment research program by number of protocols

and patient accrual 42

4-7. NCI-PAHO collaborative cancer treatment research program by location and number of

active protocols 44

7-1. National Library of Medicine non-U. S. MEDLARS Centers 67

A-1. Total expenditures for NIH international programs, by activity and BID, FY 1982 120

A-2. NIH international research and research training awards by country /area and mechanism,

FY 1982 122

A-3. NIH international research and research training awards, FY 1947-82 126

Figure

1. NIH Organization Chart 10

A-1. NIH international activities, funding by mechanism, FY 1982 117

A-2. NIH international research and research training awards, FY 1973-82 118

A-3. NIH international research and research training awards, FY 1973-82 119

Chapter I

Overview of International Activities

International activities relevant to the mis-
sions of the Bureaus, Institutes, and Divisions
(bid's) are described in their separate chapters.
This chapter highlights features of these activ-
ities that overarch the special roles of the NIH
components, those that involve other agencies in
the Public Health Service (PHS), other executive
departments (e.g., Department of State), and
such multilateral organizations as the World
Health Organization (WHO) and the Pan Ameri-
can Health Organization (PAHO).

The breadth and complexity of NIH interna-
tional activities are clearly illustrated in the
sections on bilateral agreements in the BID
chapters of this report and especially in the
section containing the report of the Fogarty
International Center (FIC) that describes its
international coordination and liaison activities.
These agreements, which are links between
foreign and U.S. Governments, are usually es-
tablished through the Department of State. The
biomedical programs may be part of broad sci-
ence and technology agreements or of more
specific health agreements. As of 1982, the NIH
was participating in over 39 bilateral agreements
involving 29 countries, the most recent additions
being Kuwait and Nigeria (1981) and Finland
(1982). Because numerous Institutes (in some
instances as many as 9 or 10) and other PHS
components participate in agreements with a
given country, the liaison function of the FIC
contributes to smooth coordination of complex
relationships. The FIC may also initiate rela-
tionships with countries (coordinated with the
State Department) and may involve appropriate
BID'S, depending on the nature of the scientific
or disease area involved. The bilateral agree-
ments have been of great value in reducing
social and political barriers to scientific ex-
changes, in capitalizing on unique features of
local environments and resources, and in foster-
ing collaborative undertakings with shared tech-
nical and professional resources and shared costs.

Another source of funds for collaborative
efforts is the Special Foreign Currency (P.L.
'tSO) Program. As discussed in more detail in the
report on the FIC International Research and
Awards Programs, this source of support is being
replaced, in most cases, by matching funds.
These funds are administered by joint boards

established by the United States and the foreign
country. The joint boards review and monitor
individual projects of mutual interest.

All categorical components of the NIH, as well
as the FIC, work closely with multilateral organ-
izations, especially the WHO. The FIC coordi-
nates NIH advice for the Department of Health
and Human Services (DHHS) and its represen-
tation to the WHO concerning agenda, budget,
and policy issues.

During FY 1982, the FIC was designated as the
first WHO Collaborating Center for Research
and Training in Biomedicine. This designation,
which is for a 'f-year period, provides a new kind
of opportunity for the United States (via the
NIH) to expand its leadership role in interna-
tional biomedical sciences. Activities in the
planning stage include expanded information
exchange and strengthened linkages with coun-
terpart research organizations in other countries.

An objective measure of other NIH coopera-
tion with WHO is the number of other BID's that
serve as WHO Collaborating Centers:

• The National Cancer Institute (NCI) is a
Collaborating Center for Reference on
Tumors of Laboratory Animals.

• The National Heart, Lung, and Blood In-
stitute (NHLBI) is a Collaborating Center
for Research and Training in Cardiovascular
Diseases for the Americas.

• The National Institute on Aging (NIA) is a
Collaborating Center for Joint Cooperation
on Research on-Care of the Aged.

• The National Institute of Allergy and In-
fectious Diseases (NIAID) is a Collaborating
Center for Rickettsial Reference and Re-
search, Mycoplasma Reference and Re-
search, Virus Reference and Research, and
Interferon.

• The National Institute of Dental Research
(NIDR) is a Collaborating Center for Re-
search in the Prevention of Dental Caries
and Periodontal Diseases.

• The National Institute of Environmental

Health Sciences (NIEHS) is a Collaborating
Center for Environmental Health Effects.

• The National Eye Institute (NEI) is a Col-
laborating Center for the Prevention of
Blindness.

• The National Institute of Neurological and
Communicative Disorders and Stroke
(NINCDS) is a Collaborating Center for
Research and Training in Neurosciences.

• The Division of Research Resources (DRR)
is a Collaborating Center for Reference and
Research in Simian Viruses.

• The Division of Research Services (DRS) is a
Collaborating Center for Defined Labora-
tory Animals.

The intramural NIH scientists have been a
valuable resource to the FIC, bringing their
expertise to bear when serving as nominators and
reviewers of Scholars-in-Residence, as members
of the Scholars-in-Residence Advisory Panel, or
as members of the FIC secondary review group
for Senior International Fellowships, Interna-
tional Research Fellowships, or International
Conference Awards. In turn, the FIC contributes
to the intramural programs of the NIH Institutes
through its Foreign Scientists Assistance Pro-
grams, which provide coordination, guidance, and
assistance to the BID scientific directors and to
the foreign scientists who are invited to the NIH
as Visiting Fellows, Visiting Associates, Visiting
Scientists, or Guest Researchers. In FY 1982 this
activity involved over 1,^00 scientists from over
60 countries.

Through the International Issues Study-Pro-
gram, the FIC also involves appropriate BID
scientists in studies by special task forces of
selected topics of international relevance.

More specific accomplishments under each of
these programs are described in the chapter on
the programs of the FIC.

The scientific community at the NIH and that
supported by the NIH through its extramural
programs have extensive relationships with over
60 countries worldwide. Selected scientific high-
lights of these activities are reported in the next
chapter.

Tabular and graphic summaries of NIH inter-
national actvities are presented in the appendix.
In FY 1982, $62 million of NIH's total appropri-
ation of $3.6 billion was devoted to international
activities (see table 1, Appendix). This consti-
tutes about 1.6 percent of the NIH appropriation.
This proportion has remained stable in recent
years. Of this $62 million, about $21 million, or
3^^ percent, supported scientist exchanges: for-
eign scientists conducting collaborative research
in the United States and U.S. scientists con-
ducting research abroad ($15.7 million of this

amount was devoted to the support of foreign
visiting scientists who conduct collaborative
research with intramural scientists at the NIH).
Another $11.^^ million, or 22 percent of the
amount spent on NIH international activities in
FY 1982, was devoted to support of research
grants held by foreign investigators. These
awards have been reviewed for scientific excel-
lence, for BID program relevance and priority,
and for assurance that performance in a foreign
country would yield a particular value. About
$12 million, another 17 percent, was used to
support foreign contracts that are awarded only
after competitive peer review and justification
for the conduct of the research in the foreign
country. The remainder supported international
conferences, travel, and bilateral and staff ex-
changes. Almost half of the $62 million devoted
to international programs was actually expended
in the United States on activities including sup-
port for foreign scientists and Fogarty Scholars
who study in the United States, travel, and bi-
lateral exchanges to the United States of foreign
scientists. Appendix figure 1 depicts these
activities by broad categories of program mech-
anisms.

Appendix table 2 displays the FY 1982 expend-
itures for research and research training awards,
by country or area and type of award. Most of
the foreign grants and contracts were awarded
to scientists in Canada ~ $7.^ million ~ with
scientists from Israel receiving awards in the
amount of $^A million; those from the United
Kingdom, $3.5 million; and those from Japan,
$3.^ million. Australia, Brazil, Egypt, India,
Italy, and Sweden were awarded totals of $1 mil-
lion to $3 million.

International organizations including WHO,
PAHO, and the International Agency for Re-
search on Cancer (lARC) were awarded about
$3.7 million in grants or contracts in FY 1982.

Appendix table 3 provides information on
trends of NIH international research and re-
search training awards. These activities reached
a level of $^^9 million in FY 1982. These amounts
include the $1.^ million in awards made from
Special Foreign Currency (P.L. ^80) money. This
money is appropriated to the Office of the
Assistant Secretary for Health, DHHS, and is
reviewed and administered by the NIH.

Over the past 10 years, Visiting Program sup-
port and research grants to foreign scientists
have increased to a greater extent than have
other types of international activities. The
amount devoted to international research con-
tracts remains at about $11 million. These trends
are depicted in figure 2 in the appendix. In terms
of constant 1973 dollars, however, the amount
devoted to international research and research
training awards in FY 1982 was only slightly
more ($23 million) than the FY 1973 amount of
$19.6 million. These trends are depicted in figure
3 in the appendix.

Chapter H
Highlights of Recent Scientific Advances

The following highlights present a selective
summary of scientific activities and accom-
plishments under international research pro-
grams sponsored by the Bureaus, Institutes, and
Divisions of the NIH. Drawing upon detailed
reports submitted by the BID's, this chapter
places the activities and accomplishments in the
context of global health problems and illustrates
the benefits of international collaboration in
biomedical research. Some studies between the
United States and other countries are reported
here because they employ innovative research
approaches or new technologies or examine
special populations, even though the projects are
in the early stages. They are relevant because
they are opening new paths to the solution of
health problems of international concern.

Two types of projects have been selected for
special reporting here: first, collaborative bio-
medical projects in which scientists from the
United States and at least one other country
participate to develop new knowledge that will
lead to the prevention or alleviation of diseases
or afflictive conditions; and second, epidemio-
logical studies, in which scientists, working
collaboratively, take advantage of the availa-
bility of specific cultural settings and environ-
ments in various parts of the world. These groups
have often been valuable resources for the study
of disease prevention and disease control using
epidemiologic methods of investigation. Through
their international research programs, the In-
stitutes of NIH have engaged in cooperative
epidemiologic studies with foreign countries
when particular features were eminently suitable
for learning about factors that cause or influ-
ence the course of a disease. In some instances,
a population has been exposed to environmental
factors rarely found elsewhere, or a group with a
common genetic background provides enough
individuals with a genetically determined disease
to be suitable for an epidemiologic study. In still
other instances, studies drawing on an ethnic
background make it possible to trace the influ-
ence of such factors as dietary habits, behavior
patterns, and lifestyles on the incidence and
prevalence of a disease.

Recent accomplishments and ongoing projects
of these two types of activities are described
below.

International Collaborative Projects to
Prevent or Alleviate Disease

Collaborative research between NCI scientists
and those of China on the biochemical epidemi-
ology of cancer of the esophagus has revealed
that in Linxian Province staple food is heavily
contaminated by a Fusarium genus. They have
found that T2 toxin produced by Fusarium has
both direct cytotoxic and proliferative effects
on fetal esophageal epithelium. At high dosage
of the toxin, cultured epithelial cells became
necrotic, whereas at lower doses the toxin
caused mitogenic effects including focal basal
cell hyperplasia, dysplasia, and increased num-
bers of mitoses. Atypical mitoses were also
observed. These changes are very similar to the
premalignant lesions seen in epithelium adjacent
to human esophageal carcinoma. The lead es-
tablished in China on the possible role of a fun-
gal mycotoxin in human esophageal carcino-
genesis is being pursued in a quantitative way.

By virtue of the agreement between the NCI
and the Japanese Society for the Promotion of
Science, teams of American and Japanese vir-
ologists independently isolated and identified
retroviruses that are associated with a human T
cell leukemia virus (HTLV) and the adult T cell
leukemia virus (ATLV), respectively. These are
newly identified human retroviruses, which seem
to be identical or very similar to each other. The
viruses are closely associated with mycosis fun-
goides, Sezary syndrome, and adult T cell leu-
kemia, which belong to the category of differ-
entiated T cell lymphoma and leukemia. The
viruses have been found to be endemic in the
southwestern part of Japan and certain Carib-
bean Islands.

During his sojourn in the Institute of Oncology
in Warsaw, Poland, an American pharmaceutical
chemist collaborated with Polish counterparts on
the synthesis and quality-control testing of P-32
labeled ion exchange resin microspheres for
radiation therapy of hepatic neoplasms. Repre-
sentative samples of the microspheres were
injected intraperitoneally into rats. Because of
the low uptake of the radioactive microspheres
by the liver following intraperitoneal injection, a

new approach was adapted for administration of
the microspheres. Increased absorption of the
radioactive agent occurred after delivery via a
catheter inserted into the hepatic artery. In-
formation gained from trials in experimental
animals is expected to show that a larger number
of the smaller microspheres will deliver a radi-
ation dose more exactly matching the distri-
bution of capillary blood flow. It is believed that
the radiation therapy from the beta decay of
P-32 microspheres, when combined with surgery
and/or chemotherapy, will result in a better and
longer life for the cancer patient.

A visiting Hungarian scientist, working with
his American counterpart at the Roswell Park
Memorial Institute, studied methods of tumor
cell disaggregation—mechanical and enzymic—
for yielding single cell suspensions. Among 17
tumors studied, the number of cells obtained by
disaggregation differed widely. Considering the
disaggregated samples as the starting material,
researchers found the recovery rate ranged from
30.7 to 82 percent, with a mean value of 49
percent and 56.3 percent, respectively, for
mechanically and enzymically disaggregated
samples. A high degree of separation of tumor
cells from leukocytes and red blood cells occur-
red, the separation of macrophages from tumor
cells being more difficult. Intracellular concen-
tration of the anticancer agent Ara-C and ^H-
thymidine was higher in the fractions with more
viable cells. The effect of another anticancer
agent, DDP, was opposite in that the results
suggest an intensive binding to nonviable cells.
Thus, it seems important to separate more
clearly the viable and nonviable cells to deter-
mine whether the reduced or increased uptake of
precursor or drug in nonviable cells is due to
metabolic failure or whether the nonviable cells
represent a metabolically distinct population
with preserved growth potential.

Ten American cancer centers and 13 cancer
institutes in Latin America are participating in
the Collaborative Cancer Treatment Research
Program (CCTRP) established between the NCI
and PAHO, where 26 active cancer treatment
protocols are now being investigated. Over the
total life of the program as many as 37 protocols
have been active in a single year. Eleven proto-
cols have been completed or terminated.

During the 4 years that this program has been
in full operation, 2,342 patients have been ac-
crued in the various protocols. An effective
international collaborative research program,
the CCTRP shows itself an excellent medium for
(1) promoting and practicing, at the interna-
tional level, the concept that clinical research is
the best means to prove the effectiveness of a
given treatment; (2) identifying the most satis-
factory techniques for a given trial and promot-
ing their standardized use; (3) accelerating re-
sults by pooling efforts and resources; (4) stim-
ulating the design of innovative studies attempt-

ing to solve questions of local as well as of
international interest; and (5) opening channels
of communication for the exchange of new ideas
and the comparison of results from institutional
and individual accomplishments.

As a result of exchanges between American
hosts and two visiting Soviet chemotherapists, a
protocol was drafted for a Phase I Clinical and
Pharmacologic Trial of Platinumdiammine
(CBDCA). The joint study is underway as a col-
laborative effort between the University of
Maryland Cancer Center and the All-Union On-
cologic Scientific Center in Moscow. Paralleling
the studies being pursued in the United States,
the Soviet effort includes (1) establishing the
maximum tolerable dose of CBDCA in cancer
patients; (2) evaluating CBDCA toxicity in pa-
tients with previously treated and untreated
malignancies; (3) determining the antitumor
activity of CBDCA; and (4) determining the clin-
ical pharmacokinetics of the anticancer agent.

Significant progress has been made in the
collaborative studies of the biochemical epi-
demiology of human esophageal and liver cancers
by American and Chinese scientists. Methods to
culture human esophageal and liver tissues have
been established in China. From experimental
studies, it has been determined that these tis-
sues, in culture, retain the capacity to activate
aflatoxin Bj, benzo(a)pyrene, and N-nitrosodi-
ethylamine. These and other carcinogen-DNA
adducts have been identified by high-pressure
liquid chromatography. Progress is being made as
well in establishing the conditions to culture
monolayers of human hepatic and esophageal
epithelial cells.

Collaborative research has been conducted
with personnel of the Cairo Cancer Institute
through a formal bilateral agreement with
Egypt. Recently, a Phase II study of chemother-
apeutic agents, initiated in 1976, was completed.
Twelve drugs were studied in about 400 patients
with squamous and transitional cell bilharzial
bladder carcinoma. The drugs included hexa-
methylmelamine, VM26, methotrexate, bleo-
mycin, adriamycin, platinum, Cytoxan, 5-fluor-
ouracil, trenimone, m-AMSA, vincristine, and
pentamethylmelamine. Notable response rates
were seen with hexamethylmelamine, penta-
methylmelamine, vincristine, and trenimone. On
the basis of these results, an active chemother-
apy combination might include vincristine,
pentamethylmelamine, and 5-fluorouracil. The
durable response rate after radical cystectomy
in bilharzial bladder carcinoma is 35 percent
(5-year disease-free survival), which is not im-
proved by pre- or postoperative radiotherapy.
Thus, initiation of a controlled trial of radical
cystectomy plus or minus adjuvant chemotherapy
is timely. The combination described is under
active consideration, as are other combinations.

During the course of U. S. - U. S. S. R. col-
laboration under the bilateral agreement in the

cardiovascular area, scientific progress has been
made on a number of topics. This year the tar-
geting of drugs to injured heart muscle has re-
ceived special attention.

Soviet scientists have developed synthetic
liposomes, a microscopic colloidal fat particle,
suitable for injection. In recent years, research-
ers have recognized liposomes as promising
carriers for drug transport in vivo. However, the
relatively rapid clearance of the liposomes,
which results from their capture by cells of the
reticuloendothelial system primarily in the liver,
still limited their everyday clinical use. A Soviet
investigator working with a U.S. colleague has
now succeeded in linking antibodies specific for
cardiac myosin to liposomes. When cardiac mus-
cle is damaged by lack of oxygen, unique intra-
cellular antigens are uncovered, which are rec-
ognized by this liposome-antibody complex. An
antibody-antigen interaction occurs that binds
the liposomes to the damaged cardiac muscle. By
adding an isotopic marker to the drug liposome
complex, scientists can visualize the damaged
muscle simultaneously as the therapeutic agent
is rapidly and preferentially applied to it. The
binding of the liposomes to the cardiac muscle
also slows their excretion, thereby prolonging
the efficacy of action of the drug that they are
transporting.

Sickle cell anemia is a hereditary disease that
affects 50,000 black Americans and perhaps 2
million people worldwide, mostly in Africa. This
condition results from an abnormal hemoglobin,
called hemoglobin S, which polymerizes or ag-
gregates upon deoxygenation and distorts the
blood's red cells into an elongated, sickle-like
shape. Recent research indicates that the in-
flexibility inherent in such "sickled" cells (not
the shape per se) leads to the tissue damage and
destruction of red blood cells that is charac-
teristic of this severe, and even fatal, disease.

Intramural scientists at the National Institute
of Arthritis, Diabetes, and Digestive and Kidney
Diseases (NIADDK) have conducted extensive
investigations into the polymerization process
that characterizes hemoglobin cells in sickle cell
anemia.

In the search for a therapy for this disease,
recent collaboration between investigators in
NIADDK's Laboratory of Chemical Biology and
foreign investigators has been particularly help-
ful. For instance, a Fogarty Scholar-in-Resi-
dence from Japan has provided singular ingenuity
in suggesting the synthesis of individual peptides
that might block the gelation (polymerization) of
hemoglobins. In another instance, collaboration
with a British scientist may lead to discovery of
the mechanism whereby certain peptides can
inhibit the gelation of hemoglobin.

This research could ultimately result in a
rational and effective therapy for sickle cell
anemia, both in the United States and in Africa,
and could provide an outstanding example of the

cross-fertilization that often evolves from in-
ternational scientific collaboration.

International Collaborative Projects to
Study Disease Etiology and Identify

Risk Factors

Increasingly, investigators are convinced that
to prevent or minimize the adverse effects of
environmental factors, adequate methodologies
to predict the toxicity of these environmental
factors must be developed. NIEHS scientists,
through multilateral and bilateral agreements in
collaboration with scientists throughout the
world, have played a leading role in assessing
current methods and developing better method-
ologies for assessing the toxic potential of en-
vironmental chemicals. Major emphasis has been
placed on international collaboration aimed at
developing better short-term methods for de-
tecting whether chemicals can cause such toxic
effects as genetic mutations, birth defects, and
damage to various organ systems. For example,
recent remarkable advances in the fields of
genetics and mutagenesis have revolutionized
the fields of toxicology and carcinogenesis by
providing new short-term test methods to reveal
whether chemical substances can damage DNA.
Detection of damage to DNA has important
implications for carcinogenesis and heritable
genetic diseases. Clearly, a number of factors
interact to determine the ultimate action of
chemical mutagens and carcinogens. Under the
U.S.-3apan Cooperative Medical Sciences Pro-
gram, Japanese and American scientists have
successfully identified dietary factors capable of
enhancing or inhibiting the mutagenic activity of
substances found in food. For example, muta-
genic and carcinogenic compounds from broiled
fish and ground beef have been isolated and
identified. Additional tests are being conducted
with a variety of other foods that can reduce the
activity of the mutagens in cooked meats. These
studies may eventually lead to the prevention of
cancer and genetic diseases in which diet is a
contributing factor.

Exposure to physical environmental factors
has also become of growing concern as the num-
ber of emission sources has increased. Under the
U.S.-U.S.S.R. Medical Science and Public Health
Agreement, joint studies on the biological ef-
fects of microwave radiation, and static and low
frequency electromagnetic fields are underway.
Now that a detailed protocol for a duplicate
experiment has been developed, both sides will
compare the same behavioral, electrophysio-
logical, and biochemical methods under exposure
conditions as identical as possible. The purpose is
to determine, first, whether both groups will

observe the same effects and, second, which
methods appear to be the most sensitive. It is
hoped that this study will provide insights into
the reasons why Soviet scientists generally re-
port effects of electromagnetic waves on the
nervous system at exposure levels below those
reported in the United States.

The impact of migration on cardiovascular
disease is an important public health concern.
After studying variations in motivations and
personal characteristics of migrants and nonmi-
grants, scientists have discovered significant
differences in disease patterns. Filipino mi-
grants, for instance, experience higher risk of
hypertension and death due to cardiovascular
disease after migration to Hawaii or California.
Similar increases were reported for Japanese
migrants to these areas. Although hypertension
is a major health problem in both Asians and
Europeans, in Asians the most prevalent sequela
is stroke, while in Europeans heart attack is the
most frequent outcome. The changing risk ex-
perienced by Asian migrants to westernized
areas indicates a large environmental factor in
the etiology of cardiovascular disease. Yet, the
process of westernization has resulted in con-
flicting patterns of cardiovascular disease in
different countries. In the Philippines this proc-
ess, which includes a Western diet, is accompan-
ied by an increased risk of coronary heart dis-
ease, while in Japan coronary heart disease is
decreasing in spite of westernization and in-
creased consumption of saturated fats. Examin-
ation of these differences may uncover clues to
the relative importance of the various known
risk factors in the etiology of cardiovascular
disease. More important, it may lead to further
decrease in cardiovascular disease through a
lessening or elimination of these risk factors.

An extremely high incidence of Huntington's
disease (HD) exists among certain residents
around Lake Maracaibo in Venezuela, all report-
edly descended from a Spanish sailor who arrived
in the country in 1860. Scientists at the Univer-
sity of Zulia in Maracaibo are working with
NINCDS scientists and grantees on a study of
over 200 HD patients in the area and 2,000 of
their relatives.

Since these Venezuelans have all inherited an
identical HD gene, they are particularly valuable
subjects for research. In addition, several fami-
lies have intermarried, creating the possibility
that some descendants may carry two genes for
HD. These features make this community unique
in the world. No one knows whether such a
"double dose" of the gene would be lethal to the
fetus or would greatly shorten the life of any
child born alive; however, if individuals carrying
two genes for HD can be found, they would be
ideal subjects for studying the precise metabolic
abnormality arising from the defective gene.

In 1981 and 1982, the NINCDS conducted two
scientific expeditions in Venezuela. Venezuelan

HD patients and at-risk family members were
examined neurologically and psychologically,
were filmed to document clinical status, and
were administered medical history question-
naires. Blood and skin samples have been taken
from over 260 patients, family members, and
controls and have been sent to NINCDS grantees
for analysis. The Venezuelan pedigrees collected
so far have been computerized and are now part
of an NINCDS-supported Huntington's Disease
Research Roster at the University of Indiana.

Grantees using the Venezuelan cell lines are
generating "maps" identifying the location of the
patients' genes on the chromosomes. These maps
will be useful for locating any defective gene
causing inherited disease, as well as for under-
standing normal inheritance. This research, on
the forefront of neurogenetic investigations,
holds tremendous promise, not only for con-
trolling Huntington's disease, but also for al-
leviating suffering worldwide.

In FY 1982, the NINCDS continued to expand
its program in neuroepidemiology, a major por-
tion of which entails collaboration with sci-
entists and health workers in other countries.

The failure of governments and health agen-
cies in most developing countries to measure
accurately the extent of various disorders cre-
ates a serious problem. Many have few resources
for such measurement and no usable data. To
begin to meet this need, the NINCDS and WHO
have developed a screening examination and
questionnaire that can be used by lay health
workers and have joined with health officials to
pilot test the examination and questionnaire in
Nigeria, Mexico, and China. The examination and
questionnaire are designed specifically to find
cases of cerebrovascular disease, epilepsy, ex-
trapyramidal disorders, brain tumors, peripheral
neuropathies, and migraine headache. They are
also designed to facilitate statistical compari-
sons among countries. Two interesting prelimi-
nary findings have come from the early data:
rural Nigerian populations have a prevalence of
migraine headaches similar to residents of major
U.S. and European cities; and China has the
highest prevalence of cerebrovascular disease of
any country in the world where the problem has
been studied. The NINCDS, WHO, and officials in
China, Nigeria, and Mexico are now planning the
project's second phase, which will study possible
risk factors. A third and final phase should de-
termine the best methods of control and pre-
vention.

A number of other countries— including Peru,
Colombia, Venezuela, Kenya, India, and Sene-
gal—are adapting the questionnaire and exami-
nation for their own purposes.

The NIA, still in the first decade of develop-
ment, continues to participate in activities that
promote general scientific cooperation among
national institutes and programs of gerontology
around the world. Outstanding research projects

of high scientific merit that are particularly
relevant to NIA programs are in some cases
more directly supported by the Institute.

One such example is a collaborative project
the Institute has developed with a French expert
on studies relating to dihydroepiandrosterone
(DHEA). Worldwide interest in this naturally
occurring hormone is increasing, because the
DHEA level decreases with age and abnormal
levels are observed in many pathological states.
Research results and theoretical interpretations
of these results vary considerably and tend to be
quite controversial.

Because it is important to understand the
relationship of this hormone to the aging proc-
ess, the NIA Biomedical Research and Clinical
Medicine Program has entered into a cooperative
arrangement with a well-known investigator
from the University of Paris to examine natu-
rcilly occurring levels of DHEA in the tissues of
mice and rats supplied from NIA colonies of aged
animals. These analyses are expected to yield
important information to the NIA on the value of
mice and rats as models for DHEA research and
at the same time contribute to the investigator's
DHEA research program in France.

The populations in the Pacific region and the
health impact of their migration to the United
States offer a wide range of opportunities to
extend our knowledge of how environmental and
genetic factors interact to influence cardio-
vascular disease patterns. In order to explore and
evaluate these scientific opportunities, the
NHLBI held an international workshop on the
Changing Patterns in Cardiovascular Disease in
the Pacific Basin, in January 1982. Data were
presented from the following countries and re-
gions: China, Taiwan, the Philippines, Australia,
New Zealand, Micronesia, Hawaii, other islands
of the South Pacific, and the WHO Region for
the Western Pacific. The scientists recommend-
ed that these unique opportunities for special-
ized studies in the Pacific region be exploited to
the utmost. To take advantage of already avail-
able baseline information and disease prevalence
data, investigators must complete incidence
followup examinations in the Guam and Palau
survey populations and the California cohort of
the NI-HON-SAN Study (Japanese living in
Japan, Hawaii, and California). Standardized
surveillance of cardiovascular disease trends and
risk factors needs to continue in Fiji, the Phil-
ippine Islands, and several Pacific Island groups
where cardiovascular disease and associated risk
factors appear to be increasing. New insights
into the relative roles of the environment and
genetics in the etiology of cardiovascular disease
may result from studies of the causes of urban-
rural differences in the Philippines and Fiji and
of serum cholesterol levels in Japan, the North-
South differences in hypertension prevalence in
China and Japan, the different coronary heart
disease mortality rates among migrants and

nonmigrants in Australia, and the different risk
of cardiovascular disease among Indians and
Fijians in Fiji.

Because sudden infant death syndrome occurs
primarily during sleep, a better understanding is
needed of the effects of development on sleep
cycles and of the interaction between the sleep
cycle and respiratory activity. Studies underway
in Australia using immature and adult marsupi-
als, called potoroos, will help to determine de-
velopmental characteristics of respiratory con-
trol during sleep. Because marsupial offspring
are born at a very early stage of development
and continue developing in the marsupial pouch,
this particular animal offers the unique advant-
age of easy access to young mammals at stages
corresponding to the fetal or intrauterine periods
in other species.

In the Dominican Republic, investigators sup-
ported by the National Institute of Child Health
and Human Development (NICHD) have been
working with a pediatrician to study an unusual
group of Dominican children who are born ge-
netically male, but because of a congenital en-
zyme deficiency (5-alpha-reductase), their ex-
ternal genitals appear to be female.

At the time of puberty, these children who
have been raised as girls suddenly act like boys:
a dramatic switch of gender role occurs even
without phallic development. This complete
sexual reversal clearly demonstrates that gender
identity is not fixed in early childhood and that
testosterone profoundly affects the brain at the
time of puberty in establishing male identity and
behavior patterns. These discoveries have im-
portant implications for the therapy of children
who are born with other kinds of sexually am-
biguous genitalia.

In Asia a cross-cultural study of the factors
that determine the timing of first births has
revealed the apparent universality of the effects
of socioeconomic variables, such as education or
rural/urban origins, on the timing. In Asian
societies as dissimilar as Hong Kong and the
Philippines, these variables have the same ef-
fect; yet the importance of cultural heritage
remains.

After other factors are taken into account,
the Confucian heritage groups have substantially
later ages at first birth than the Muslim and
Hindu groups, with substantially younger ages at
first birth. The study also has shown that in-
creases in age at marriage found in many de-
veloping countries have not had so great an
impact on reducing fertility as once thought. In
general, the later the age at marriage, the
sooner the first birth occurs and the higher the
level of early marital fertility.

Two researchers from Brock University in
Canada have collaborated with the Physical
Sciences Laboratory of the DCRT in studying the
theory and measurement of intermolecular
forces. This project has succeeded, for the first

time, in directly measuring the force between distance, as well as elucidating the effect of

biological macromolecules, providing a good structure on this force. An extension of the work

picture of how the force between parallel DNA will allow the determination of important ther-

helices behaves in response to changes in modynamic parameters of proteins.

Compomnis
ofHeMi

Figure 1.— NIH organization chart

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
PUBLIC HEALTH SERVICE
NATIONAL INSTITUTES OF HEALTH

Deputy Director for
Intramural Research

/yyyyVy Associate Director for ^^TT/y^
yyyyyy; International Research /Vyyyy
////////////////////////////A

Deputy Director for Extramural
Research and Training

Associate Director for Program
Planning and Evaluation

Director

Associate Director for Medical
Applications of Research

Associate Director for
Administration

Deputy Director

Associate Director for
Clinical Care

Associate Director for
Communications

Assistant Director for
Intramural Affairs

Associate Director for
Research Services

Bureaus

National
Cancer Institute

National Heart,

Lung, & Blood

Institute

National Institute of

Arthritis, Diabetes, &

Digestive & Kidney

Diseases

National Library
of Medicine

National Institutes

Aging

Allergy &
Infectious Diseases

Child Health &
Human Development

Environmental
Health Sciences

Eye

General
Medical Sciences

Dental
Research

Neurological &

Communicative

Disorders & Stroke

Research & Support Divisions

Clinical
Center

Research
Grants

Computer Research
& Technology

Research
Resources

Research
Services

Chapter HI
John E. Fogarty International Center
for Advanced Study in the Health Sciences

Introduction

The Fogarty International Center for Advanced
Study in the Health Sciences (FIC) was created
in 1968 to provide a focus and organizational
mechanism for NIH activities in international
biomedical research. The mission and objectives
of the FIC are to:

• Facilitate the assembly of scientists and
leaders in the biomedical, behavioral, and
related fields for discussion, study, and re-
search relating to the development of sci-
ence internationally as it pertains to health
and its implications and applications for the
future;

• Further international cooperation and col-
laboration in the life sciences through its
research programs, conferences, and
seminars;

• Provide postdoctorate fellowships for
training in the United States and abroad and
promote senior scientist exchanges between
the United States and other countries;

• Coordinate NIH activities and functions
generally concerned with health sciences at
an international level; and

• Serve as a focal point for foreign visitors to
the National Institutes of Health.

The Director, FIC, is also the NIH Associate
Director for International Research, in which
capacity he advises the Director of the NIH on
the development of international policies and
procedures related to health. On international
issues the FIC interacts with each of the BID's
of the NIH, as well as with other components of
the Department of Health and Human Services.
In addition, the FIC maintains liaison with the
Department of State and other Government
agencies, with foreign embassies, and with mul-
tinational and foreign organizations.

The FIC discharges its responsibilities through
four program activities: Advanced International

Studies, Foreign Scientists Assistance, Interna-
tional Research and Awards, and International
Coordination and Liaison. The FIC also provides
core support for the Gorgas Memorial Labora-
tory in Panama.

During FY 1982, the FIC was designated as the
first WHO Collaborating Center for Research
and Training in Biomedicine for a l^-year period.
The FIC has begun to fulfill its role as a WHO
Collaborating Center by expanding its informa-
tion exchange activities and linkages with coun-
terpart research organizations in other countries.

Additional FIC program highlights during FY
1982 were the initiation of a Nominating Com-
mittee for the International Research Fellowship
(IRF) Program in China, the reactivation of the
IRF Nominating Committee in the West Indies,
and the negotiation of an agreement between the
FIC and the Alexander von Humboldt Foundation
in the Federal Republic of Germany for the FIC
to announce the availability of German fellow-
ships for U.S. scientists.

Specific program activities and accomplish-
ments are presented in the following sections.

Advanced International Studies

The goal of Advanced International Studies
Programs is to facilitate international scientific
communications by providing international for-
ums for the exchange of scientific information
and for the review and evaluation of major areas
of biomedical research, particularly as related to
international health problems of mission interest
to the National Institutes of Health.

Advanced international studies in the health
sciences are aided through three FIC inter-
related programs: International Issues Study-
Program, International Conferences and Semi-
nars Program, and Scholars-in-Residence Pro-
gram. The fundamental purpose of these pro-
grams is to review and evaluate recent research
results and the derivative knowledge so that the
best directions for further scientific research to
overcome or avoid major health problems will be
apparent. These activities tap scientific talent,
not only throughout the United States, but also

in any country in the world where it exists. The
major goal of these programs is to evaluate and
transfer new knowledge and technologies to or-
ganizations and individuals to whom the new
information will be useful.

International Issues Study-Program

This program effort is devoted to harnessing
the best pertinent health science talent in the
world to analyze major health problems of mul-
ticountry interest and to give advice and guid-
ance to national health authorities on actions to
be taken, individually and collectively, to over-
come the problems. Issues addressed include in-
ternational aspects of biomedical and behavioral
research, research manpower training, and the
transfer of research results to bring new know-
ledge to bear where it will benefit health
worldwide.

Identification of aspects of the problem cal-
ling for further research is of paramount interest
in each project. Some projects are described
below.

International Conference on the Eradication of
Infectious Diseases

Published in the Sept.-Oct. 1982 (Vol. ^, No. 5)
issue of Reviews of Infectious Diseases were the
proceedings of the International Conference on
the Eradication of Infectious Diseases, con-
ducted by the FIC and a number of other agen-
cies in May 1980. At that conference the par-
ticipants analyzed the nature of the program
activities that led to the world eradication of
smallpox. With those procedures in mind, they
then determined their applicability to other in-
fectious diseases. Among the recommendations
stemming from that evaluation were separate,
indepth analyses of measles, poliomyelitis, and
yaws. The FIC has moved to accomplish these
analyses, each with the relevant national and
international health-related agencies.

International Symposium on Measles
Immunization

Conducted in March 1982, this international
symposium accommodated the enthusiastic par-
ticipation of scientists from many parts of the
world. During the assessment of the current im-
pact of measles on the world population, par-
ticipants gave particular attention to comparing
countries with and without special vaccination
programs, discussed strategies for the attain-
ment of a high level of immunization, and eval-
uated prospects for eventual eradication. They
identified aspects of the disease and of its con-
trol that need further research. The participants
concluded that the challenge is to exploit the

available vaccines and to overcome the remain-
ing economic, logistic, and attitudinal barriers.
Participants returned home resolved to eliminate
measles as a universal cause of childhood misery
and of long-term disabilities. Proceedings of the
symposium were submitted for publication in
Reviews of Infectious Diseases .

International Symposium on Poliomyelitis Control

Extensive plans were made for this project,
which is scheduled for March [^-17, 1983, in the
Headquarters Building of the Pan American
Health Organization. The focus of the sympo-
sium will be on control of poliomyelitis by means
of immunization. Applicable to future programs
to advance such control in both developed and
developing countries, these recommendations
will be based on assessment of up-to-date know-
ledge concerning the viruses themselves, the
current status of poliomyelitis in various parts of
the world, and the vaccines now available. Con-
sideration will be given to political, economic,
and administrative aspects as they impede or
facilitate immunization strategies and to the
feasibility of elimination of paralytic poliomye-
litis in the foreseeable future. Emphasis will also
be on identification of research needs and on
new developments and their potential contri-
bution to improved vaccines. This project is
being jointly sponsored by the FIC, NIAID,
NICHD, and NINCDS of the NIH; Centers for
Disease Control, PHS; National Center for Drugs
and Biologies, Food and Drug Administration
(FDA); U.S. Agency for International Develop-
ment; Institute of Medicine, U.S. National
Academy of Sciences; WHO; PAHO; American
Public Health Association; Infectious Diseases
Society of America; National Foundation for
Infectious Diseases; The Rockefeller Foundation;
Merieux Institute, Inc.; Smith KlineRIT; Lederle
Laboratories; and Hoechst Aktiengesellschaft.

International Symposium on Yaws Control

Planning occurred during 1982 for this sympo-
sium, which is scheduled for November or De-
cember 1983. It will involve scientists from all
the tropical and subtropical areas of the world
and, in total, the discussions will cover all three
endemic treponematoses: yaws, pinta, and en-
demic syphilis. The main purpose of the sympo-
sium will be to assess the current impact of yaws
and of yaws control efforts in the world; to re-
view current technology and strategies relevant
to control of yaws; and to consider the feasi-
bility of yaws eradication. Aspects of this dis-
ease and its control that need further research
will be identified. The proceedings of the sym-
posium will be submitted for publication in a
journal of broad readership, e.g.. Reviews of
Infectious Diseases.

Internationa] Conferences and Seminars Program

The International Conferences and Seminars
Program fosters advanced international studies
in the health sciences through scientific meet-
ings and conferences that provide opportunities
for biomedical and behavioral scientists from
various parts of the world to share their know-
ledge, ideas, and concerns about international
health issues and to discuss current and future
research endeavors and problems.

Good scientific communications are funda-
mental to a productive biomedical research
program and to effective practical use of the
results of biomedical research. Therefore, the
FIC places a high priority on the planning and
conduct, or funding support, of scientific sym-
posia, conferences, and workshops. These FIC-
supported meetings are of two types: intramural
and grant supported. In FY 1982, the FIC pro-
vided partial or total funding support for 8 in-
tramural conferences and partial funding support
for ^8 grant-supported conferences.

Intramural conferences are arranged by
Fogarty Scholars as well as by NIH intramural
scientists and FIC staff. The subjects of these
meetings are of broad scientific interest and
draw outstanding scientists from many parts of
the world as participants. In FY 1982, the FIC
supported one intramural conference. Catechol
Estrogens, organized by the Director of the NIH
Clinical Center. The remainder were organized
by Fogarty Scholars alone or in conjunction with
NIH intramural scientists. These conferences are
described in the subsequent section on the
Scholars-in-Residence Program.

Grant-supported conferences are initiated by
non-NIH scientists who seek funding through
grant applications. The NIH Division of Research
Grants receives these applications, which are
often given multi-Institute assignments accord-
ing to their specific scientific nature. For those
applications that are international in nature or
have an international aspect, the FIC joins with
the other assigned Institutes in the review of the
applications and their funding, if approved. Ex-
amples of conferences supported by the FIC in
FY 1982 follow.

VI International Symposium on Atherosclerosis

The disease process that predisposes indi-
viduals to heart attacks and stroke is athero-
sclerosis (hardening of the arteries). Restriction
of blood circulation due to atherosclerosis de-
prives the heart and other organs of necessary
oxygen and nutrients. Vital arteries are narrowed
by mounds or plaques on the inside wall in a
process that may take years and is associated
with a number of risk factors. The most impor-
tant putative risks are excessive blood choles-
terol in the form of elevated low-density lipo-

proteins, high blood pressure, and cigarette
smoking.

Hardening of the arteries is the basic cause of
coronary artery disease, the major cause of
death in America. However, during the past
decade there have been a 25 percent decrease in
age-adjusted coronary heart disease and a 37
percent decrease in age-adjusted stroke mor-
tality. This reduction is probably attributable to
two factors: first, lifestyle changes reducing risk
factors and, second, improvements in care of the
patient in the acute phase just after a myocar-
dial infarction.

The FIC and the NHLBI provided sponsorship
and partial funding support for the VI Interna-
tional Symposium on Atherosclerosis, which
convened in West Berlin in 3uly 1982.

The general theme of the symposium, which
attracted more than 1,500 scientists from many
countries, was the causes and prevention of
atherosclerosis and its complications. The pros-
pect for preventive cardiology seems bright. The
decline in heart disease in America and the as-
sociated clear evidence of changing lifestyles
due to a decrease in the use of tobacco products,
a reduction in the consumption of high saturated
fat/high cholesterol foods, an awareness of the
benefits of physical exercise, control of obesity
and hypertension, all suggest an encouraging
trend. However, heart disease remains a major
problem.

The scientific program focused on the most
basic aspects of the disease process. The pro-
ceedings of the symposium will be published, and
it is expected that this volume will be a valuable
source of information concerning progress in
atherosclerosis research.

Fifth International Symposium on Human
Chlamydial Infections

Human chlamydial infections are transmitted
from person to person by sexual contact. Serious
health consequences result, affecting not only
male and female partners, but also newborn
infants. In the United States it is estimated that
25,000 cases of pneumonia and 50,000 eye
infections in infants are caused yearly by
Chlamydia .

Chlamydial infections are the most prevalent
of the sexually transmitted pathogens. Pelvic
inflammatory disease is the most serious com-
plication from chlamydial and gonorrheal in-
fections, causing sterility and ectopic pregnan-
cies with possible fatal consequences to mothers.
Pelvic inflammatory disease often causes dam-
age to the female reproductive tract, resulting
in about 50,000 major surgical procedures each
year in the United States.

European scientists are at the forefront of the
clinical and epidemiological research and control
aspects of chlamydial infections. The FIC and
the NIAID joined in providing partial funding

Table 3-i.— Scholars-in-Residence, 1982

Scholar's name and country

Discipline and home institution

Date of Date of
arrival departure

Shmuel Shaltiel, Israel

Tomas Hokf elt, Sweden

Klaus Kuhn

Federal Republic of Germany

Samuel Barondes, United States

Franklin Bunn, United States

David Shemin, United States

Rolf Luft, Sweden

Herman Kalckar, United States

Irwin Gunsalus, United States

Helmut Holzer, Fed. Rep. of Germany

Howard Schachman, United States

Theodor Wieland, Fed. Rep. of Germany

M. Manago-Grunberg, France

Bracha Ramot, Israel

Hsiang-Tung Chang, China

Gaetano Salvatore, Italy

G. P. Talwar, India

Sanford Palay, United States
Mordechai Sokolovsky, Israel
Lars Svennerholm, Sweden

Keith Porter, United States
Frits Orskov, Denmark
Susan Lowey, United States
Frank Fenner, Australia

Biochemistry

Weizmann Institute of Science

Neurobiology, Karolinska Institutet

Biochemistry

Max Planck Institute for Biochemistry

Psychiatry, Univ. of California, San Diego

Hematology, Peter Bent Brigham Hospital

Biochemistry, Northwestern University

Endocrinology, Karolinska Institutet

Biochemistry, Boston Univ. Grad School

Biochemistry, University of Illinois

Biochemistry, University of Frieberg

Biochemistry, Univ. California, Berkeley

Biochemistry, Max Planck Institute

Biochemistry

Institut de Biologie Physico-Chimique

Hematology

The Chaim Sheba Medical Center

Neurophysiology, Shanghia Brain Research
Institute, Acad. Sinica

Endocrinology

Istituto di Patologia Generale

Biochemistry

All India Institute of Medical Science

Anatomy, Harvard Medical School

Biochemistry, Tel Aviv University

Neurobiology, Psychiatric Res. Center
Gothenburg University

Cell Biology, University of Colorado

Microbiology, Int'l Excherichia Centre

Biochemistry, Brandeis University

Virology, Australian National University

08/2^81 0^2^/82

09/01/81

06/15/82

10/01/81

09/30/82

10/01/81

12/31/81

01/01/82

03/31/82

01/01/82

04/01/82

02/01/82

04/30/82

02/01/82

04/30/82

02/11/82

04/30/82

02/15/82

05/15/82

0^/01/82

06/30/82

04/01/82

06/26/82

04/01/82

08/07/82

04/20/82 05/30/82

05/01/82
06/14/82

08/30/82
09/24/82

06/30/82 09/30/82

07/01/82
07/01/82
08/23/82

09/01/82
09/10/82
09/13/82
09/16/82

09/01/82
12/22/82
12/22/82

12/15/82
12/15/82
12/13/82
02/16/83

support for a meeting in Sweden in June 1982.
Scientists from North America, seven European
countries, South Africa, and Malaysia partici-
pated. Recognizing that research on the molec-
ular biology of Chlamydia is not well advanced
and that a need exists for greater knowledge of
the structure and function of this pathogen, in-
vestigators believe that a better understanding
could aid in improving diagnostic techniques,
which are absolutely necessary to combat the
infection.

Recent advances in hybridoma technology, as
well as in standard classical immunochemical
methods, were reported at the symposium and
gave a clearer picture of the surface antigens of
Chlamydia . It is hoped that these advances will
lead to better diagnostic methods. Genetic
studies using recombinant DNA technology were
presented. The meeting also covered perinatal
infections and maternal complications, eye dis-
eases, and preventive and control measures.

The Third World Conference on Lung Cancer

Smoking is associated with lung cancer and a
host of other diseases, including cancers of the
oral cavity, pharynx, larynx, esophagus, pan-
creas, and bladder. Smoking is also related to
heart and blood vessel diseases, chronic bron-
chitis and emphysema, respiratory infections,
and stomach ulcers. In summary, smoking is the
single most important preventable cause of
death and disease in our nation.

If present trends in smoking continue in the
United States, lung cancer will probably be not
only the leading cause of cancer death among
men, but also among women.

Lung cancer is an international health prob-
lem. The FIC and the NCI provided sponsorship
and partial funding for the Third World Confer-
ence on Lung Cancer held in Tokyo, Japan, in
May 1982. Representatives of 27 nations served
on the international program committee. The
conference itself addressed a broad range of
topics including prevention of lung cancer. The
epidemiology, carcinogenesis, early diagnosis and
staging, pathology, surgery, radiotherapy, immu-
notherapy, cellular kinetics, and lung tumor
markers were actively discussed.

The conference theme was a succinct evalu-
ation of current knowledge related to preven-
tion, diagnosis, and treatment of lung cancer,
focusing on both the causes of failure and the
successful ingredients in the various program
areas. Emphasis was placed on new approaches
supported by ideas that evolved from the in-
teraction among specialists from different
countries.

Fourth International Symposium on
Nasopharyngeal Carcinoma

The causes of cancer have been the focus for
much biomedical research in the past few

decades. The varying components of lifestyle,
e.g., nutrition, environmental factors, are being
analyzed to identify and classify significant risk
factors. (A risk factor increases the incidence of
a specific disease and provides an opportunity
for disease prevention by intervention or by
elimination of the factor.)

Nasopharyngeal carcinoma is a malignant
neoplasm that has its origin at the surface epi-
thelium of the nasopharynx. This cancer has
attracted worldwide attention because of the
evidence suggesting that multiple factors, in-
cluding environmental, genetic, and viral,
interact in the etiology of this medically inter-
esting disease.

The FIC and the NCI provided sponsorship and
partial funding support for a symposium on naso-
pharyngeal carcinoma held in Kuala Lumpur,
Malaysia, in September 1982. Malaysia and the
surrounding areas in Southeast Asia (Singapore,
Hong Kong, China, and Taiwan) have a high in-
cidence of this disease. Participants discussed
the various facets of the disease: clinical, epi-
demiological, virologic, immunologic, and ge-
netic, as well as treatment and prevention. Diet,
chemical carcinogens, and infectious agents
were examined. A wealth of evidence from
studies from many countries implicates the
Epstein-Barr virus. (This virus, extremely com-
mon in the human population, is clearly the
cause of infectious mononucleosis.) The virus is
thought to act in concert with other factors,
such as immune depression and genetic factors.

Scholars-in-Residence Program

The purpose of the Scholars-in-Residence
Program is to enable established scientists and
scholars interested in international health to
exchange information and ideas with other sci-
entists and scholars through preparation of a
book, monograph, or other report, as well as
through meetings and workshops, and to col-
laborate in research in an environment conducive
to innovative approaches to international health
issues.

Scholars-in-Residence are nominated by NIH
scientists or former Fogarty Scholars. A Scholars
Advisory Panel of senior intramural scientists
reviews the nominees, after which approved
nominees are invited by the FIC as openings in
the program become available.

Since 1970, 100 Scholars from 21 countries
have participated in the program. During FY
1982, 25 Scholars participated for varying per-
iods of time, as shown in table 3-1. The average
stay of the Scholars was 3 months, with 21
Scholars being in residence 6 months or less, 2
Scholars for 8 months, and 2 Scholars for 10 or
12 months each.

The following two situations illustrate the way
the Fogarty Scholars interact and share their

extensive knowledge with NIH scientists:

• Professor Giorgio Bernard! used the first
two terms of his scholarship to work in the
Laboratory of Biochemistry, NCI, where he
collaborated with the laboratory chief.
Professor Bernardi is one of the interna-
tional leaders in the field of gene structure
at the molecular level. Much of his work is
concerned with so-called "repetitive se-
quences" in DNA. The significance of the
regulation and expression of DNA in health
and disease is just beginning to be under-
stood, but it is suspected that they are in-
volved in modulating genetic information
during development and tissue differenti-
ation. Knowledge of this process may have
implications for understanding tumor
growth. Professor Bernardi's lifelong work
has been concerned with the structure of
large molecules such as proteins and nucleic
acids. He has contributed to the methodol-
ogy of this field that is important for much
of contemporary molecular biology.

The benefit to the NIH of Professor
Bernardi's residency has been his presence
in a major laboratory, his organization of
the conference on "Highly Repeated DNA
Sequences in Eukaryotes" (in collaboration
with his host laboratory chief at the NCI,
and attended by leading researchers in
molecular biology and genetics), and the
opportunity afforded him to reflect on the
meaning of work done over many years.

• Professor Lars Svennerholm is a world
authority on neurochemistry. Dr. Svenner-
holm has described many of the formal
components of brain and nervous tissue,
such as gangliosides and other fat soluble
compounds of sugar and fatty acids. These
compounds have been shown to be important
as parts of receptors that build antigens.
There are reports that measles virus nu-
cleotide sequelae are found in multiple
sclerosis plaques from patients dying of MS.
During his stay at the NIH, Professor Sven-
nerholm initiated collaborative investigation
of the hypothesis that gangliosides may be
involved in formation of human brain lesions
since other investigators have discovered
that gangliosides produce neurological
symptoms in animals. A three-way collabo-
ration began between the neurochemistry
laboratory headed by Svennerholm in Got-
henburg, Sweden, the VA Hospital and
UCLA in Los Angeles, and Svennerholm's
NIH associates. The discovery that gangli-
osides (sugar-containing lipids) are recep-
tors, or attachment sites, for various bac-
terial toxins and viruses, will have applica-
tion to the study of cancer, influenza, and
other diarrheal diseases.

The FIC scholarship played a key role by
permitting Professor Svennerholm to extend
his research through collaboration with U.S.
scientists. This episode in Svennerholm's
career exemplifies the kind of benefit that
can be achieved from an extensive period of
direct scientist-to-scientist interaction.

Scholars-in-Residence are provided an oppor-
tunity to organize scientific meetings and work-
shops during their residency at the NIH. Some
examples follow.

• During Professor Svennerholm's residency at
the NIH, in collaboration with colleagues
from the NINCDS and the NIADDK, he
organized an International Workshop on
Gangliosides, which was held at the NIH in
December 1981. This workshop brought
together researchers in virology, oncology,
biochemistry, immunology, and genetics.

• Structure and Regulation of Connective
Tissue Genes. This meeting was organized
by FIC Scholar Dr. Klaus Kuhn, Max Planck
Institute of Biochemistry, Munich, with
scientists from the NIDR, the NHLBI, and
the NCI. The first session considered the
structure of genes; the second was devoted
to human genes and genetic disorders; and
the last dealt with regulation of collagen
gene expression. Dr. Kuhn expects to publish
a report on the conference in 1 983.

• Coexistence of Neuroactive Substances in
Neurons. The proceedings of this confer-
ence—which was arranged by FIC Scholar
Dr. Sanford Palay, professor of neuroanat-
omy at Harvard, and a colleague—will be
published in 1983 by Springer.

Other Scholars interacted with their fellow
scientists at the NIH in similar ways. Dr.
Barondes, for example, spent time with members
of the NCI Molecular Biology Laboratory,
studying behavior of slime mold cells when they
touch each other. For neuroscience, the study of
how slime molds reproduce has implications for
behavior of nerve cells, how they grow and
organize themselves into networks during
development.

During 1982, there were several publications
by Scholars who had completed their scholarships
in previous years. One such publication, Recent
Advances in Mucosal Immunity , Raven Press,
1982, is the report of a meeting organized by
Lars Hanson, one of the editors and major con-
tributors who based his contributions to this
effort on work performed at the NIH and in
Sweden, analyzing results obtained in field
studies in Pakistan on diarrheal disease in
malnourished children. Dr. Hanson, who is pro-
fessor of clinical immunology at Gothenburg,

continues his association with FIC activities and
will participate in an FIC meeting on polio-
myelitis.

The Scholars, whose interests touch on pro-
grams of every BID, also participate regularly in
intramural research seminars conducted by the
Senior Science Advisor to the Director, NIH. In
addition, they give their own lectures and semi-
nars. A partial list of those that took place dur-
ing FY 1982 follows:

• Regulation of the Cellular Response to
Hormones: Signal Propagations and Attenu-
ation (Dr. Shmuel Shaltiel)

• Accretion of Gangliosides in the Brain
During Development (Dr. Lars Svennerholm)

• Hydrophobic Chromatography Use in the
Resolution and Purification of Proteins and
Cells (Dr. Shmuel Shaltiel)

• Hydrophobic Chromatography: Proposed
Mechanism and Its Relevance to Biorecog-
nition (Dr. Shmuel Shaltiel)

Other conferences organized through collabor-
ation between FIC Scholars and NIH intramural
scientists were:

• Workshop on Hemoglobin Assembly and
Catabolism. Organized by Professor
Franklin Bunn, of Harvard University (while
a Fogarty Scholar-in-Residence), in con-
junction with an intramural scientist from
the NIADDK, this workshop investigated the
problems of hemoglobin and hemoglobin-
related inherited blood diseases. These
diseases include thalassemia (in which too
little hemoglobin is produced), which results
in anemia. Abnormal hemoglobins (the
oxygen-carrying portion of the red blood
cell) are a serious health problem through-
out the world; recently developed technol-
ogy for growing erythroid cells and other
new tools of molecular biology provide new
research opportunities for understanding the
normal and the diseased states.

• International Workshop on the Influence of
the Environment on Leukemia and Lym-
phoma Subtypes. Organized by FIC Scholar
Dr. Bracha Ramot, professor of medicine at
Tel Aviv University, this meeting brought
together experts from around the world to
discuss the epidemiology of lymphoid neo-
plasia in the light of modern immunological
concepts of these diseases.

• Translational/Transcriptional Regulation of
Gene Expression. This conference was
organized by FIC Scholar-in-Residence Dr.
Marianne Grunberg-Manago, professor of

biology at the Institute of Biology in Paris.
She and a colleague at the NHLBI, Dr. Brian
Safer, edited the proceedings, which were
published by Elsevier in September 1982.

• Endogenous Lectins May Play Many Roles
(Dr. Samuel Barondes)

• The Structure of CoUagens and Errors in
Their Macromolecular Organization in Some
Connective Tissue Diseases (Dr. Klaus Kuhn)

• Metabolic Interconversion of Fructose
Biphorphatase in Yeast (Dr. Helmut Kolzer)

• An Approach to Diabetes Health Care in
Sweden (Dr. Rolf Luft)

• Immunological Approaches to the Control of
Fertility (Dr. G.P. Talwar)

• Muscarinic Receptors in the Endocrine
System (Dr. Mordechai Sokolovsky)

Fogarty Scholars-in-Residence and NIH
intramural scientists also collaborate in the
arrangement and presentation of seminars. Of
the 12 seminars that took place in FY 1982, the
following are illustrative: "Mechanisms for Syn-
thesis and Inactivation of Peptides," "Molecular
Mechanisms of Brain Receptors," "The Coopera-
tive Oxygenation of Hemoglobin," "Red Cells
Are Not Created Equal: The Consequences for
Sickle Cell Anemia and Malaria," "Chemical
Mechanisms of Action of Insulin," and "Dual
Information Coding in Retinal Ganglion Cells:
Small Eye Movements and Visual Acuity."

Foreign Scientists Assistance

The Foreign Scientists Assistance Programs of
the FIC provide coordination, guidance, and
facilitative services to the NIH BID's in the
administrative management of the NIH Visiting
Program and the NIH Guest Researchers Pro-
gram. These programs offer the opportunity for
talented scientists throughout the world to en-
gage in collaborative research with NIH sci-
entists. Through these programs, the NIH is able
to take advantage of the research services of
over 1,400 scientists from about 60 countries.
The FIC staff also supports visiting programs of
the National Center for Drugs and Biologies
(NCDB) of the FDA, and the National Institute
of Mental Health (NIMH) and the National
Institute on Alcohol Abuse and Alcoholism
(NIAAA) of the Alcohol, Drug Abuse, and Mental
Health Administration (ADAMHA).

Under the NIH Visiting Program, foreign
researchers are invited to NIH laboratories by a

senior investigator and usually stay from 1 to 3
years. The relationship between the NIH scien-
tific community and its foreign colleagues is
based on mutual benefits; the Visiting Program is
both a learning and a sharing process whereby
benefits accrue to each side. Foreign scientists
join NIH laboratories for a limited time to meet
programmatic needs and are provided the op-
portunity to explore promising leads—with lim-
ited investment from the NIH. The foreign sci-
entists enjoy enhanced capability from exposure
to modern research methods for effective re-
search in their chosen fields upon return to their
home institutions.

The NIH Visiting Program has three levels:
Visiting Fellow, Visiting Associate, and Visiting
Scientist. The Visiting Fellows, those whose
postdoctoral experience in medicine or health
science does not exceed 3 years, receive awards
for advanced research experience. Their scien-
tific potential comes to the attention of NIH
senior investigators through their presentations
at meetings, workshops, etc., and through their
contributions to scientific literature. The mid-
level Visiting Associates have between 3 and 6
years of postdoctoral experience and the neces-
sary knowledge to further a particular study. At
the top level are the Visiting Scientists with
more than 6 years of postdoctoral experience
and exceptional abilities that enable them to
make a significant contribution to the ongoing
research of the sponsoring BID. Like Visiting
Associates, Visiting Scientists are appointed for
the performance of services for the NIH. In all
instances awards and appointments are made on
an invitational basis only.

The total NIH Visiting Program participation
for all BID'S (including NIMH and NIAAA of
ADAMHA and FDA's NCDB) served by the For-
eign Scientists Assistance Programs in FY 1982
was 1,523 individuals, including 1,093 foreign
scientists from 56 countries. There were 7^9
Visiting Fellows, 192 Visiting Associates, and 152
Visiting Scientists at a cost of $17.2 million of
intramural research funds, an increase of 268
individuals over the FY 1981 total of 1,255 and
an increase in total funding of $IA million.

In addition to administering the NIH Visiting
Program, the Foreign Scientists /assistance Pro-
grams provide advisory services in varying de-
grees, particularly in immigration matters, to
other foreign scientists at the NIH. In FY 1982
the Foreign Scientists Assistance Programs
assisted 430 other foreign scientists of whom 77
percent were Guest Researchers, who are usually
funded from sources within their home countries;
10 percent were appointed as special experts
funded by the BID's; and 13 percent represented
scientists on bilateral agreements, FIC Inter-
national Research Fellows located at the NIH,
and Fogarty Scholars.

Most of these foreign scientists were from
Europe and Asia, with a number from the Latin

and other North American countries, and the
African and Middle Eastern countries.

Illustrative descriptions of projects in which
Visiting Scientists and Foreign Guest Research-
ers have been involved are provided throughout
this report, in the sections that describe each of
the BID programs.

International Research and Awards

Several types of international fellowship pro-
grams are supported fully or partially by the FIC
and are administered by the FIC. These programs
facilitate the exchange of research experiences
and information by enabling foreign scientists to
pursue their research interests in U.S. labora-
tories or, conversely, by providing opportunities
for U.S. researchers to work in foreign labora-
tories. These programs are:

• International Research Fellowships,

• WHO/NINCDS/FIC International Neuro-
sciences Fellowships,

• WHO/NIAID International Tropical Diseases
Fellowships, and

• Senior International Fellowships.

Listed below are four other fellowship pro-
grams for U.S. scientists to study abroad, ad-
ministered by the FIC but supported by the Gov-
ernments of France, the Federal Republic of
Germany, Sweden, and Switzerland:

• French National Institute of Health
(INSERM) Fellowships,

• Alexander von Humboldt Foundation Fel-
lowships,

• Swedish Medical Research Council Fellow-
ships, and

• Swiss National Science Foundation Fellow-
ships.

Under individual cooperative agreements, the
FIC administers health scientist exchange pro-
grams with five countries: France (CNRS),
Poland, Romania, the U.S.S.R., and Yugoslavia.
NIH participation in the Special Foreign Cur-
rency (P.L. ^&0) Program is administered by the
International Research and Awards Programs.
Each of these programs is discussed in detail in
the following section.

International Research Fellowships

The International Research Fellowship (IRF)
Program provides opportunities for postdoctoral

biomedical or behavioral scientists in the form-
ative stages of their research careers to extend
their research experiences in a laboratory in the
United States. These fellowships forge rela-
tionships between distinguished U.S. scientists
and qualified scientists in other countries to
resolve health-related problems of mutual
interest.

During FY 1982, there were ^7 participating
countries with Nominating Committees. Thirty-
four Nominating Committees recommended 127
applicants for the program. Subsequent to sci-
entific peer review conducted by the NIH, 9^ (78
percent) were funded. Recipient countries of
fellowship awards are shown in table 3-2.

Table 3-2.— International research fellowship
awards by country /area of applicants, 1 982

Americas

Europe

Argentina

Austria

Brazil

Belgium

Chile

Denmark

Mexico

Finland

Peru

France

Uruguay

Ireland

Italy

Netherlands

Africa

Norway

Nigeria

Poland

Sudan

Spain

Sweden

Asia and Far East

Switzerland

Australia

United Kingdom

India

Yugoslavia

Japan

Korea

Middle East

New Zealand

Israel

Taiwan

Lebanon

In FY 1982, a Nominating Committee was
formed in China, and the Nominating Committee
in the West Indies was reactivated. Applications
are expected from these committees in Septem-
ber 1983.

Examples of collaborative research activities
undertaken by IRF awardees are described in the
following section.

• Renal involvement in systematic lupus
erythematosus (SLE) is characterized by
many different clinical and morphological
features. To evaluate the effects of treat-
ment and the prognosis on different types of
SLE, an IRF awardee working with a sci-
entist from Columbia University determined
the frequency and amount of immune com-
plex deposits in the tubular basement mem-
brane and in the interstitium from autopsy
cases of renal nephritis. These findings were

correlated with (1) the degree and type of
interstitial inflammation, interstitial edema
and fibrosis and tubular atrophy; (2) the
type, severity, and activity of glomerular
lesions; (3) the degree of renal functional
impairment; and (4) the long-term prog-
nosis. The results indicate that, in renal
biopsies from patients with lupus nephritis,
tubular basement membrane and intersti-
tium deposits are usually associated with
more severe and active glomerular disease.
Renal insufficiency is more common and
more pronounced in these patients, and the
long-term prognosis is considerably worse.
Renal function was reasonably good in 65
percent of the cases in patients with tubular
basement membrane deposits ^ years after
the original biopsy in contrast to about 85
percent for patients without these deposits.
These findings are of potential significance
for selection of the most appropriate ther-
apy in these patients.

• Subjecting premature babies to oxygeri-
enriched breathing mixtures can result in
retrolental fibroplasia or retinopathy of
prematurity. The high-oxygen concentration
inhibits normal development of the retinal
vessels by constricting them, which leads to
vasoproliferation. Using the cat as an ani-
mal model for retinopathy, one IRF awardee
working with a scientist from Duke Uni-
versity was able to determine the contri-
butions of oxygen levels in the choroid and
the iris under different physiologic and
pathologic conditions. This information with
further experimentation can be used to
understand the various factors or changes
that take place to produce dilation or con-
striction of blood vessels, the changes that
cause retinopathy of prematurity.

• Diabetes mellitus, which is the fifth leading
cause of death in the United States, has
been diagnosed in over 5 million Americans
and probably affects an additional 5 million
people. Several lines of evidence suggest an
involvement of the immune system in the
etiology of insulin-dependent diabetes mel-
litus. One IRF awardee in collaboration with
an NIH intramural scientist studied the
capacity of islet cell surface antibodies to
lyse human beta cells as well as other islet
cells. The Fellow demonstrated that islet
cell surface antibodies react with different
antigens on the pancreatic islet cells and
that therefore these antibodies are hetero-
geneous in nature. Some of the islet cell
antibodies and the islet cell surface anti-
bodies are cytotoxic for islet cells; thus,
these antibodies may play a role in the
pathogenesis of insulin-dependent diabetes
mellitus. This research also demonstrated

that islet cell IgM antibodies can often be
detected in the area of prediabetic first-
degree relatives of patients with insulin-
dependent diabetes mellitus and gestational
diabetes (30 percent and ^6 percent, re-
spectively).

International Neurosciences Fellowships

The International Neurosciences Fellowship
Program was established in 1977 in cooperation
with the NINCDS and WHO and is administered
by the FIC with funds provided by NINCDS.
Three awards were made in FY 1982 to scientists
in China.

International Tropical Diseases Research Fellowships

Table 3-3.~Senior International Fellowship
awards by country of destination

Americas

Europe 25

Canada

France 2*

Chile

Federal Republic
of Germany 1

Asia and Far East

Italy ^*

Australia

Sweden 2
Switzerland li

Middle East

United Kingdom 12

Israel

*Two scientists have collaborative research
projects in two countries.

The FIC in cooperation with the National
Institute of Allergy and Infectious Diseases and
with the United Nations Development Program
(UNDP)/World Bank/WHO Special Program for
Research and Training in Tropical Diseases has
established a limited number of postdoctoral
fellowships in tropical diseases. Candidates for
these fellowships are from countries in which the
following diseases are endemic: malaria, schis-
tosomiasis, leishmaniasis, trypanosomiasis, fil-
ariasis, and leprosy. Two awards jointly funded
by the FIC and the NIAID in FY 1982 and were
made to scientists from China and Egypt.

Senior International Fellowships

The Senior International Fellowship (SIF) Pro-
gram provides opportunities for established
biomedical or behavioral researchers to do col-
laborative research in a foreign institution. SIF's
enhance the exchange of ideas and information
about the latest advances in specific areas of
medicine, both basic and clinical. They also lead
to improvement in the research, education, and
clinical potential of U.S. nominating institutions,
which profit from the scientists' experiences
abroad. During FY 1982, U.S. institutions nomi-
nated 71 scientists for SIF's. Of this number, 29
(^1 percent) were funded. Table 3-3 lists the host
countries that received SIF awardees.

Examples of collaborative research projects
undertaken by SIF awardees include:

• Widespread in the population, herpesvirus
infections are responsible for oral and gen-
ital infections and for such infections as
chickenpox and shingles. This virus is not
now controlled by vaccinations. Develop-
ment of suitable herpesvirus vaccines will
require the identification and production of
the protective antigens. An SIF awardee in

collaboration with a scientist from the
Institute of Medical Microbiology in the
Federal Republic of Germany studied the
frequency of cytotoxic T lymphocyte pre-
cursors in lymphoid population from normal
mice and from mice infected with live her-
pesvirus or vaccinated with inactivated
herpesvirus. The Fellow was able to show
that only mice exposed to live herpesvirus
developed large numbers of cytotoxic T
lymphocyte precusors and that inactivated
virus vaccine was a poor stimulation of such
cells.

Since the cytotoxic T lymphocyte re-
sponse is considered important in immunity,
these results would indicate that if inacti-
vated herpesvirus is to be used as a vaccine,
a suitable and safe adjuvant that can stim-
ulate adequate cytotoxic T lymphocyte
responses may be identified.

• Researchers have shown that in the rat
model of streptozotocin-induced diabetes
mellitus, the disease can be treated by
transplantation of fetal pancreas. The major
obstacle remaining before general appli-
cation of this method is the problem of
rejection. An SIF awardee and a scientist
from the Walter and Eliza Hall Institute in
Australia explored methods to prevent re-
jection of transplanted fetal pancreas al-
lographs using the rat and pig as animal
models. Several methods proved partially
effective in diminishing rejection of ailo-
graphed pancreas: (1) prolonged culture (3
weeks) of fetal tissue in 95 percent oxygen;
(2) collagenase digestion of pancreas fol-
lowed by short-term (k days) culture of
tissue; (3) oral administration of cyclosporin
A; and (^) ultraviolet treatment of donor
spleen cells.

• Detection of small amounts of biomolecules
is a challenge to scientists who are studying
molecules present in small amounts in var-
ious organs or body fluids. One SIF awardee,
in collaboration with a scientist from the
Imperial College of Science and Technology
in England, attempted to develop a new
methodology for sequence analysis of nano-
mole or less amounts of specific proteins. In
one project, using a newly developed ioni-
zation technique of fast atom bombardment
and a high field magnet sector mass spec-
trometer, the awardee was able to show
that in the dephosphorylation of casein (a
milk protein), the dephosphorylation pro-
ceeds with high specificity and sequentially
removes up to five phosphate groups from
serine residues. This methodology can be
used to elucidate biochemical structures
such as the various neuropeptides.

Special Emphasis Senior International
Fellowship Programs

These programs have the same purpose and
eligibility criteria as the SIF Program. Since
these programs are administered by the FIC in
cooperation with the NIADDK and the NINCDS,
the emphasis is on arthritis, diabetes, and epi-
lepsy. During 1982, no awards were made in
these programs.

Foreign Government Fellowships

Currently four countries provide fellowships
for U.S. scientists to conduct research abroad:
France, the Federal Republic of Germany, Swe-
den, and Switzerland. These are sponsored, re-
spectively, by INSERM, the Alexander von Hum-
boldt Foundation, the Swedish Medical Research
Council, and the National Science Foundation of
Switzerland, The FIC publicizes these programs
and advises prospective applicants about the
programs. With the exception of the Alexander
von Humboldt Fellowship applications, the NIH
reviews the applications for scientific merit and,
afterwards, the FIC forwards the applications
and summary statements to the appropriate
awarding agency to make the funding decisions,
whereas the Alexander von Humboldt Foundation
reviews all its own applications. In FY 1982
three applications were funded under the Swe-
dish program and five under the Swiss.

Individual Health Scientist Exchange Programs

The FIC, on behalf of the Public Health Ser-
vice, administers Individual Health Scientist
Exchange Programs with France, Hungary, Po-
land, Romania, the U.S.S.R., and Yugoslavia. The

exchange programs, whose basic goal is to ex-
pand and disseminate scientific knowledge, fos-
ter new research ideas through the promotion of
scientist-to-scientist contacts. As components of
broader intergovernmental bilateral agree-
ments for cooperation in science and technology,
including health, these programs serve the broad
range of health interests of the PHS and the
respective foreign ministries of health. They
provide opportunities for health professionals to
become familiar with various aspects of public
health and biomedical research activities of the
participating host country. By providing support
for short- and long-term exchanges, the pro-
grams encourage and facilitate direct collabo-
ration and communication between health and
biomedical communities of the United States and
the participating countries.

Under an agreement between the NIH and the
CNRS, the two institutions support the work of
U.S. scientists in French laboratories and the
work of French scientists in U.S. laboratories for
periods of 6 to 12 months. The type of activity
undertaken with a host laboratory may include
the conduct of basic or clinical research, famil-
iarization with or utilization of special tech-
niques and equipment not otherwise available,
and/or related cooperative efforts. Each side
supports 75 person-months of work annually.
During FY 1982, 9 U.S. scientists worked in
French laboratories, and 1 1 French scientists
worked in U.S. laboratories.

Under an overall science and technology
agreement with Hungary, a Program of Cooper-
ation and Exchanges that was initiated in FY
1982 now provides for individual health scientist
exchanges up to 12 months from each country.

• Under these programs, during FY 1982,
three Polish scientists visited the United
States for familiarization with vascular and
abdominal surgery, surgical treatment of
tracheal strictures, and micro and laser
surgery in ophthalmology.

• Four Romanian scientists spent varying
periods of time at U.S. universities with
research interests in the following areas:
electron microscopy, cancer, recent ad-
vances in understanding pain, and surgery of
the spine.

• A six-member team of American neuro-
surgeons visited the Soviet Union to study
research in new computerized CT scanning
procedures and stereotactic computerized
methods for treatment and removal of cen-
tral nervous system lesions. During this
visit, the delegation discussed and ex-
changed information on problems inherent in
this method and on the neurobehavioral
effects on behavior before and after ster-
eotactic removal.

• One American scientist visited Moscow and
Leningrad to study clinical and research
work in otolaryngology. Several Soviet sci-
entists interested in such diverse topics as
immunology, interferon research, eye sur-
gery, neurosurgery, and artificial organs
visited the United States in FY 1982.

• Activities under the U.S.-Soviet Health
Exchange Program were suspended mid-year
in order to evaluate the program. The FIC is
attempting to identify areas of excellence
in Soviet science to encourage greater U.S.
participation. Activities are expected to
resume in FY 1983.

• Four Yugoslav health scientists visited the
United States to study various phases of
hospital administration and nursing.

Table 3-^ provides summary data on these
exchange programs.

Special Foreign Currency Program

Using unique financial resources, the Special
Foreign Currency (P.L. 'fSO) Program supports
biomedical research, translation, and dissemi-
nation of information in the health sciences in
selected countries. In India and Pakistan, U.S.-

owned "excess foreign currencies" are used. In
Poland and Yugoslavia, U.S.-owned "near excess
foreign currencies" appropriated to the Depart-
ment of State are deposited in joint funds where
they are matched by the foreign country. In
Egypt, negotiation of an analogous source of
funds is underway but not completed. Admini-
stered by joint boards, these funds are allocated
to the NIH and to other agencies to support
biomedical research of mutual interest to the
United States and Poland or Yugoslavia.

These foreign currencies cannot be exchanged
for U.S. dollars or other convertible currencies,
nor can funds be used without the consent of the
foreign government. Central National Coordi-
nating Committees, in addition to joint boards on
which the United States is represented, review
technical merit and ascertain concurrence with
national policies, procedures, and priorities on
health and scientific issues and take into account
political, economic, and other factors.

The program is collaborative in character.
Research proposals must represent a joint effort
of U.S. and foreign scientists within their areas
of professional interest and competence and in
conformity with national priorities. The program
comprises projects covering a wide spectrum of
biomedical and health sciences. Attempts are
made to draw upon resources unique to the host
country, such as cultural, ethnic, anthropolog-
ical, ecological, and disease patterns. Promising

Table 3-(f.— Rate of exchange of U.S. and foreign scientists since
initiation of international research and awards programs

Average

FY 1982

Total U.S.

U.S.

Other

Total country

Maximum

length of

scientists

Date

(man-mo

stay

to country

to U.S.

to country

to U.S.

Country

initiated

per year)

(man-mo)

no. m-m

1 no.

m-m

(man-mo)

France

1979

9.5

10 53

132

18^.5

(CNRS)

Hungary

1982

none

Poland

1979

3.5

none

5.5

60.5

Romania

1967

none

6.5

30.5

U.S.S.R.

1961

20*

2.0

7 3

309

536.5

Yugoslavia

1 979 unspecified

2.3

none

3.5

*The FIC instituted a moratorium on this exchange program during FY 1982. As of January 1983, the
program has been resumed with a maximum of 5 man-months per country.

projects concerned with investigation of the
more fundamental aspects of biomedical prob-
lems as well as clinical and behavioral science
investigations and epidemiological studies are
represented in the program.

India

In India, the Working Group on Medical and
Health Sciences of the Joint Commission on
Economic, Commercial, Scientific, Technologi-
cal, Educational and Cultural Cooperation,
established by a bilateral agreement signed
October 28, 197^, has shaped and guided the
collaboration with the NIH in recent years. The
Fifth Meeting of the Subcommission in 1980 was
notable for its shift from the repeated emphasis
of previous meetings upon indigenous infectious
and parasitic diseases of primary interest to the
Indian Council of Medical Research and Ministry
of Health (tuberculosis, leprosy, streptococcal
infections, diarrheal agents, hepatitis, enceph-
alitis, malaria, filariasis, leishmaniasis) to the
inclusion of interests in molecular and cellular
biology. With the intervention of the Department
of Science and Technology in the Sixth Meeting
of the Subcommission in December 1981, the
trend toward modern biological sciences was
reflected by changing the name to the Working
Group on Life Sciences, Medical and Health
Sciences and by designating a subgroup on medi-
cal and health sciences and a subgroup on life
sciences. The latter was to stimulate research in
modern biology, genetic engineering, interferon,
chemo-receptor physiology, and macromolecular
dynamics.

Pakistan

At present no projects are active in Pakistan.
The past program has been modest in size as
judged by the number of projects. There is
neither a science and technology nor a health
agreement between the United States or its
agencies in Pakistan. The Director General of
the Pakistan Medical Research Council visited
the NIH in FY 1982. During the discussions, such
areas of mutual interests were identified as
cancer, infectious disease, immunology, and
training, which can serve as the basis for col-
laboration as clinical centers under construction
in Pakistan are completed.

Poland

The Polish program, initiated by the U.S.-
Polish 3oint Committee for Cooperation in the
Field of Health, was established in 1962 and for
several years has had as its areas of primary
interests and priorities cancer, cardiovascular
disease, occupational health, maternal and child
heeilth, rehabilitation, neurosciences, metabolic
and endocrine disturbances, organ transplanta-

tion and nephrology, and health protection or-
ganization. The collaborative program experi-
enced a major disruption in FY 1982 for the first
time since its inception as a result of the ter-
mination of the Science and Technology Agree-
ment and the sanctions imposed upon Poland.

With the establishment in recent years of the
U.S. -Polish Joint Board on Scientific and Tech-
nological Cooperation and its Marie Sklodowska
Joint Fund, the U.S. -Polish Joint Committee for
Cooperation in the Field of Health, although
established earlier under a separate agreement,
became a virtual subsidiary as the result of the
joint fund's support of health projects. The
agreement that established and maintained the
joint board and its joint fund was scheduled for
renewal before its expiration date of December
31, 1981. To replenish the resources of the joint
fund, the Department of State was planning to
provide $2 million in zlotys annually from its
appropriation beginning in FY 1982 for a subse-
quent 5-year period to be matched equally by the
Polish Government. Prevailing economic condi-
tions were such that the Polish side found it
necessary to negotiate for a portion of the de-
posits to be made in dollars for basic scientific
supplies. During the resulting delay in negotia-
tions, martial law intervened. Then sanctions
were imposed as the result of the expulsion of
the U.S. Science Attache, and the agreement
authorizing the joint board lapsed. Although
there are uncommitted funds apportioned for
biomedical and health sciences in the joint fund,
their availability remains indeterminate.

Yugoslavia

The present Yugoslavia program is under the
auspices of the U.S.-Yugoslavia Joint Board on
Scientific and Technological Cooperation, which
includes the health sciences. In contrast to other
joint boards, no list of priority areas has been
developed for the collaborative program in
Yugoslavia. A delegation of Yugoslav scientists
visited the United States at the time the joint
board was established to identify productive
areas for collaboration. The topics suggested
were medicine, biology, cardiovascular disease
(especially hypertension), malignancy (including
etiology, pathology, therapy, and immunology),
neurosciences, hemoglobinopathy, immunology,
drug toxicity, and occupational diseases. The
program, as it has developed, includes many of
these topics. In addition, the Republics ordinarily
propose projects in keeping with their individual
local priorities and emphasize economic devel-
opment and short-term applicability.

The Yugoslav side usually submits a list of
15-25 health science proposals, received from
the science organizations in the several Repub-
lics of Yugoslavia. The U.S. researchers and
institutions also submit proposals. The joint
board meets twice a year at which time it re-

views these proposals and selects projects to be
funded. The joint fund is replenished annually by
equal matching deposits of dinars, in the total
amount of $3.^^ million, with the U.S. deposit
made by the Department of State from its ap-
propriation. The DHHS is allotted 11 percent of
this money, which is used to fund the selected
projects from the various PHS agencies.

Egypt

In Egypt the U.S.-Egypt Joint Working Group
on Health Cooperation and its Subcommittee for
Biomedical Research, Infectious and Parasitic
Diseases has had a major role in shaping the
U.S.-Egyptian collaboration. Under its direction
the NIH program underwent a transition from
investigator-conceived projects representing
academically oriented research interests to
mission-oriented projects directed at national
health goals: namely, raising citizens' health
awareness; reducing infant, child, and maternal
mortality rates; and reducing birth rates. Popu-
lation groups for special attention are infants,
children of school age and under, mothers,
workers, the aged, low income, and medically
underserved. In addition to undergoing a review
to determine the potential for immediate con-
tributions to the objectives and populations,
projects are also evaluated for their contribution
to such collateral aspects of importance as
institution building, manpower training, and
interrelationships with other projects.

The last meeting of the 3oint Working Group
and its committees was held in June 1981. The
remaining excess currency funds available to the
NIH were committed at the end of FY 1981. The
proposed Multisector Science and Technology
Project expected to provide funds for FY 1982
and the subsequent 3 years was not approved.
This project was to be supported by the USAID
with matching funds from the Government of
Egypt and funds from Title III of P.L. i+SO, which
formerly funded the Special Foreign Currency
Program under the authorization of Title I.
Authorization for use of funds from this latter
source has not been provided. At a planning
meeting of representatives of the Joint Working
Group in August 1982 in Cairo, concern was
expressed about the lack of action on the Multi-
sector Science and Technology Project. During
the subsequent visit to the United States by the
Minister of Health of Egypt, the status of the
existing collaboration was reviewed and plans
were made for a meeting of the Joint Working
Group on Health Cooperation to be held in 1983.

Scientific Accomplishments

The program in Egypt has, however, achieved
some noteworthy scientific gains. For example,
it fostered the development of the eye disease
and blindness research center at the University

of Alexandria in collaboration with the Proctor
Foundation for research in ophthalmology of the
University of California. This center evolved
from a blindness registry and epidemiological
studies that have shown that t^.7 percent of the
rural population and 1.5 percent of the urban
population in Northern Egypt have significant
visual disability. At least half of the loss of
vision in rural areas and one-third in urban areas
is due to prevalent ophthalmias and infectious
diseases that are treatable and preventable. This
study has also established the role of Chlamydia ,
the causative agent of trachoma, in bronchitis,
pneumonias and diarrheal diseases, which ac-
count for an excessive mortality among Egyptian
children.

A molecular biology study at the Indian In-
stitute of Science in Bangalore, India, has pro-
duced a number of theoretical conformations of
DNA, among them a "left-handed molecule,"
which was in contradiction to contemporary
thought but in subsequent experimental studies
by scientists in the United States was found to
occur naturally. Such information is a key to the
understanding of biological processes and has
application to prevention and treatment of ge-
netic diseases.

The National Library of Medicine's Critical
Review Program for writing and publishing re-
views of health science topics in Poland has
produced a number of widely accepted publica-
tions. A review of "Human Neutrophils" brought
together the findings and concepts of the bril-
liant hematologic school in Krakow and of other
Polish hematology schools. A summary of the
biology of the human neutrophilic granulocyte, a
white blood cell, is given with emphasis upon the
clinical significance, especially of the non-
specific resistance of people to various microbial
agents and the recent research evidence of the
role of neutrophiles in antitumor immunity.
Another Polish review, "Industrial Noise Pollu-
tion and Hearing Impairment," is a product of
this program and is intended for audiologists,
otolaryngologists, industrial health officers, and
others such as physiatrists who need a funda-
mental understanding of noise and hearing
problems from health, social, and economic
points of view. The topics included will be of
great interest to those involved in rehabilitation
medicine.

International Coordination and Liaison

International coordination and liaison (ICL)
activities conducted by the FIC provide for
coordination of NIH international relationships
to facilitate the interaction of scientists, to
assist in the exchange of scientific information,
and to enhance communications between the NIH
and other international offices or agencies.
These activities provide policy guidance, coor-

dination, and general oversight for the partici-
pation of the NIH with other U.S. agencies in
bilateral cooperative agreements between the
U.S. Government and other countries.

BUateral Agreements

The United States is contributing significantly
toward the resolution of a broad spectrum of
international health problems through its do-
mestic research and related efforts, its cooper-
ative health relationships with other countries,
and its participation in the programs and activ-
ities of international organizations, notably WHO
and PAHO. Formal intergovernmental agree-
ments may take a variety of forms, ranging from
those of broad scope for educational, cultural,
and scientific exchange to more specific ones in
science and technology or the health fields. In
some instances, a health agreement may be
subsidiary to a broader agreement in science and
technology. Less formal technical level agree-
ments may also exist directly between counter-
part institutes for a specific purpose. As a basis
for cooperation in particular situations and cir-
cumstances, formal agreements often use special
resources or form a basis for surmounting con-
straints of different social and political systems.

Coordination of NIH participation in all bi-
lateral agreements that involve NIH components
and scientists is a continuing responsibility of
the FIC. The Assistant Secretary for Health has
now designated the NIH as the lead admini-
strative agency for bilateral programs with
Belgium, France, the Federal Republic of Ger-
many, Hungary, 3apan, Poland, Romania, Vene-
zuela, and Yugoslavia. Accordingly, ICL staff
carry out this role for the NIH.

During the last decade, international health
research and related activities conducted by
DHHS/PHS, and particularly by the NIH, have
increasingly been planned collaborative efforts
and have been instituted through special bilat-
eral arrangements. Since the first formal pro-
gram was signed with 3apan in 1965, more than
20 bilateral health agreements have been signed
directly between DHHS officials and officials of
foreign ministries of health.

At present there are ^2 agreements that in-
volve the NIH with 26 countries, among which
are China, Egypt, the Federal Republic of Ger-
many, India, Israel, Japan, Nigeria, the U.S.S.R.,
and various countries of Eastern Europe. The
NIH participates with the following countries in
broad agreements covering science and tech-
nology cooperation for which the Department of
State or the National Science Foundation serves
as the executive agency: Egypt, France, India,
Israel, Italy, 3apan, Nigeria, Pakistan, Poland,
Romania, Spain, Venezuela, and Yugoslavia. The
NIH occasionally participates in agreements with
Argentina, Australia, Brazil, Greece, Kenya,

Mexico, Senegal, and Zimbabwe. Although the
FIC has a role in the administration of bilateral
agreements, the scientific content of the proj-
ects supported in foreign countries is selected by
the collaborating scientists at the NIH in coop-
eration with the foreign scientists.

Significant events that occurred during FY
1982 included:

• The U.S.-P.R.C. Joint Science and Tech-
nology Commission Meeting, which was held
in Washington on October 15-17, 1981. The
Joint Commission governs the agreement
under which the Health Protocol operates.
The Health Protocol continues to be very
active with exchanges of U.S. and Chinese
scientists in the areas of cancer (NCI),
infectious diseases (NIAID), and cardio-
vascular epidemiology (NHLBI).

• The U.S.-Federal Republic of Germany
agreement for cooperation in biomedical
research technology, which was renewed in
September 1982 for a second 5-year term
with some small amendments. A workshop in
the cardiovascular area held in Bethesda in
October 1981 concerned cooperative ac-
tivities related to the German National
Health Survey. In July 1982, the FRG Min-
ister of Youth, Family and Health visited
the NIH.

• A Memorandum of Understanding between
the Ministry of Social Affairs and Health,
Finland, and DHHS, which has been nego-
tiated and is expected to be signed in FY
1983. The Secretary General of the Ministry
visited the NIH in October 1981 to discuss
closer cooperation in health. A draft
agreement between the NIEHS and the
Finnish Institute for Occupational Health
was developed in FY 1981.

• The U.S.-France Science and Technology
Bilateral Meeting, which took place in
Washington in September 1982. Under the
framework of the science and technology
agreement, the NIH has a cooperative pro-
gram with INSERM. Current areas of active
cooperation include cancer, respiratory
diseases, and thyroglobulin synthesis.

• The tenth meeting of the U.S.-Spain Joint
Committee for Cooperation in Science and
Technology, which was held in Washington in
May 1982. This committee, a component of
the Treaty of Friendship, provides for co-
operation in science and technology with a
recently added provision for health.

• Two agreements signed under the overall
cooperative science and technology agree-
ment with Italy : (1) by the NINCDS, in

March 1982, for collaboration in neurosci-
ences research with the National Research
Council of Italy, and (2) by the NHLBI, in
November 1981, for cooperation in cardio-
vascular diseases with the Pharmacological
Institute, University of Milam. In addition,
in November 1981 under the science and
technology agreement a workshop was held
by the NIH in Bethesda entitled "Biological
Response Modifiers," and a joint symposium
by the NHLBI, "Methods of Noninvasive
Diagnosis in Cardiovascular Disease."

• The 3uly 1982 meeting of the Joint Com-
mittee of the U.S.-3apan Cooperative Med-
ical Science Program, in Tokyo at the Min-
istry of Foreign Affairs. The 3oint Tuber-
culosis Panels and 3oint Viral Disease Panels
have begun a review that will be completed
next year. After reviewing the Leprosy and
Parasitic Disease Panels, the committee
recommended their continuation. In the
future, the Leprosy and Tuberculosis Panels
will hold combined annual meetings in view
of their common scientific interests, and
the gxiidelines for the Joint Parasitic Dis-
ease Panels will be updated to accommodate
new technologies and changing needs.

• The U.S.-Mexico meeting in Bethesda in
December 1981, which resulted in an
agreement between the PHS and the Mini-
stry of Health of Mexico to collaborate in
research and training in infectious diseases,
particularly those of children.

• The September 1982 visit to the United
States by the Indian Prime Minister, which
resulted in an agreement to establish an
Indo-U.S. Blue Ribbon Panel to enhance
science and technology cooperation between
the two countries. Areas of interest being
considered in the health field are leprosy,
immunology, and blindness prevention. The
ICL staff of the FIC work with staff of the
Office of International Health and the
Office of Science and Technology Policy in
coordinating the programs at the NIH.

Other Liaison Functions

In addition to monitoring and assisting in
bilateral activities, the ICL staff maintain
liaison with WHO and PAHO and occasionally
with other multilateral organizations, and they
provide NIH positions on agenda issues for World
Health Assemblies and PAHO and Western
Pacific Regional Organization Directing Council
meetings. ICL staff also provide material and
support for NIH participation as an observer in
meetings of the European Medical Research
Council and process requests for services of NIH

experts for WHO and PAHO committees and
other purposes.

The FIC is cooperating with PAHO in organ-
izing and sponsoring a Workshop on Research
Management Techniques for Latin American
scientist administrators. The workshop, aimed at
directors of large research institutions, research
departments of major universities, and large
public health laboratories, will be held in FY
1983.

The ICL staff assist the Institutes by review-
ing and clearing foreign travel plans and by
serving as a channel for cable communications to
and from foreign embassies and the Department
of State, by coordinating responses to inquiries
on international issues, and by processing NIH
foreign grants and contracts for clearance
through the Department of State.

The FIC Director meets periodically with the
international programs representatives of the
NIH bid's to exchange information and views on
NIH international activities and to discuss im-
plementation of related policies and procedures.

Information on NIH international activities is
collected and published in an annual report.
Special reports are prepared and made available
to NIH principals traveling to certain countries
and to officials from other countries who visit
the NIH. In addition, comprehensive briefing
books on NIH activities with various foreign
countries are produced.

A special study underway in FY 1982 was a
compilation of information on biomedical re-
search institutions in China. The report, due to
be published in FY 1983, will be available to all
interested scientists and Government officials. It
will contain names and locations of the insti-
tutions, directors and laboratory chiefs, and
recent publications from these institutions.

Gorgas Memorial Laboratory

The ICL staff also serve as the focus for U.S.
Government core support provided through the
FIC budget for the Gorgas Memorial Institute
(GMI) of Tropical and Preventive Medicine, Inc.,
and the Gorgas Memorial Laboratory (GML) in
Panama. In 1928, Congress authorized a perma-
nent annual appropriation to the Gorgas Memor-
ial Institute of Tropical and Preventive Medi-
cine, Inc., Washington, D.C., for the operation
and maintenance of a research laboratory in
Panama. This action, together with land and
building donated by the Government of Panama,
permitted the establishment of the GML. Since
FY 1971, the FIC budget has provided the annual
U.S. core support funds, which amounted to
$1.69 million in FY 1982. The FIC maintains
general program oversight for this funding.

The laboratory conducts a diversified program
of research on tropical diseases, especially those
endemic to Panama and neighboring countries.
Particular emphasis is placed on virology, par-

asitology, and the effects of environmental
change on disease vectors and transmission. Of
late, it has also undertaken studies on other
public health problems, e.g., cervical cancer and
sexually transmitted diseases. In addition to
research, it also provides special diagnostic and
reference services, epidemic investigations, and
surveillance of vector-borne diseases, and it
conducts formal and informal research training
for scientists and technicians from the United
States, Panama, and other countries. It has co-
operative arrangements with several U.S. uni-
versities for graduate and medical students.
Formal training courses in tropical medicine are
conducted several times a year for U.S. Navy
medical officers. For FY 1982, the GML had a
number of substantial scientific accomplish-
ments in the following areas:

• Ecology . The Bayano environmental eco-
logical studies indicated significant alter-
ations in insect vectors and disease poten-
tial in the area. Yellow fever surveillance
among monkey populations in the moun-
tainous areas of eastern Panama indicated a
resurgence of syl vatic yellow fever beyond
last year's limits. A manuscript on the
mammalian fauna of Panama was com-
pleted, and extensive progress has been
made on a compilation of the rodents of
Panama. Studies describing how excessive
hunting, massive deforestation, and other
ecological problems have contributed to the
disappearance of a number of valuable ani-
mal and plant species have resulted in rec-
ommendations for conservation of natural
resources.

• Vector Biology . Work in this area has ex-
panded markedly. Currently 255 animal and
avian species have been bled in the prepar-
ation of antisera for blood meal analysis.
Over 7,000 hemotophagous arthropods rep-
resenting 17 genera and 88 species of sand-
flies, mosquitoes, triatomes, and culicoides
from Central and South America have been
studied. Further study of lutzomyia sand-
flies and of man-biting black flies ( simulium
quadrivittatum ) has enabled GML scientists
to characterize these disease vectors fur-

ther, a step necessary to future vector
control efforts.

• Epidemiology . An epidemic of acute hemor-
rhagic conjunctivitis, which occurred in
Colon in 1981, was subject to a detailed
seroepidemiological study. A 53 percent
clinical attack rate was found, as well as
information on the effect of socioeconomic
level, crowding, and other parameters. A
preliminary serological study indicated 22
percent of the individuals tested had anti-
bodies for HTLV, the highest known anti-
body rate for HTLV. Further studies are
planned in collaboration with the NCI.
Haemagogus equinus mosquitoes have been
studied for their efficiency as a vector of
yellow fever. Studies have shown that St.
Louis encephalitis virus transmission is an
annual occurrence at two ecologically dis-
tinct sites in Panama, a finding that sup-
ports field data implicating the two-toed
sloth as a host for the St. Louis encephalitis
virus.

• Parasitic Diseases . Drug evaluation in the
Aotus monkey revealed two agents with
significant antimalarial activity. Success in
maintaining Plasmodium vivax for 10 days
with one subculture was recorded. Field
study in Morti, Darien Province, indicated
an endemic focus of Mansonella ozzardi
probably transmitted by simuliid flies.

• Bacteriology . Further studies on Campylo -
bacter jejuni in childhood diarrhea indicate
a high incidence in the first 6 months of
life. Antibody resistance to strains of Shi -
gella and the emergence of several new
strains have been documented. Penicillin-
resistant strains of gonococci were encoun-
tered in 12 percent of 377 prostitutes ex-
amined.

The GML is being reorganized to emphasize
tropical ecology, epidemiology, microbiology,
and clinical therapeutics. This reorganization, as
well as the consolidation of facilities, will enable
the GML to maintain a productive research
program.

Chapter IV
National Cancer Institute

The international battle against cancer offers
perhaps the best and most immediate oppor-
tunity for changing the basic quality of life for
millions of people throughout the world. The
National Cancer Institute (NCI) continues to
contribute readily to the improvement of that
quality of life because of its long tradition of
involvement in the international arena for can-
cer research. Although self-interest, on behalf of
the people of the United States, motivated NCI's
irutial concern with cancer problems in other
nations, this self-interest has been trans- formed
into a concerted international campaign in the
war on cancer. The National Cancer Act
intensified the commitment of the NCI to the
international team approach toward the control,
prevention, and ultimate eradication of cancer
as a major crippler and killer disease of a large
segment of the world's population.

By virtue of an international effort, striking
geographic and environmental variations in the
incidence and mortality of a wide range of spe-
cific organ cancers are now well recognized and,
in some instances, environmental causes have
been established for excess rates of cancer in-
cidence in certain regions of the world. For
instance, environmental factors are implicated
in the causation of a large percent of the known
cancers. The derivation of this cause-effect
relationship stems from studies in those coun-
tries of the world where the population is at low
risk for a given type of cancer, thereby estab-
lishing a "baseline" rate for that particular can-
cer type. Subsequently, a high rate of incidence
for that same cancer in other countries can be
assumed to be associated with environmental
factors. That the incidence of various types of
cancer exhibits great geographic variation is
illustrated by differences in the rate of lung
cancer incidence among men in Scotland, the
United States, and Portugal. Scotland, with the
highest rate in the world, has twice the rate for
U.S. white males, whereas the rate among Por-
tuguese males is one-seventh that of Scotland.
Again, in the Kazakh Republic of the U.S.S.R.,
the incidence of cancer of the esophagus is ex-
tremely high in regions near the Caspian Sea in
comparison to the low incidence in the extreme
eastern section of that Soviet republic.

Through its participation in activities of the
international cancer science community, the NCI
benefits from rapid advances in basic research
throughout the world and application of this new
information to the clinical management, control,
and prevention of cancer. The ultimate gain
from such collaborative cancer research efforts
of the NCI and international counterparts is a
tangible improvement in the quality and quantity
of health services available to millions of people
over the world.

The contribution of the NCI to the interna-
tional struggle against cancer includes: (1) con-
tinuing support of cancer research in foreign
countries by highly qualified scientists; (2) sup-
port of cooperative research programs, princi-
pally under bilateral agreements with foreign
governments, institutions, or organizations; (3)
maintenance of liaison and research collabora-
tion with international organizations and agen-
cies that have well-defined objectives in cancer
research and cancer prevention; W support of
training of foreign scientists in the United States
as well as of the interaction of American sci-
entists with colleagues in foreign laboratories;
and (5) management and operation of an Inter-
national Cancer Research Data Bank for pro-
moting and facilitating, on a worldwide basis,
the exchange of information for cancer research,
care and management of patients, and cancer
control and/or prevention.

Summan of International Programs
and Activities

Bilateral Agreements and Other
Countn-to-Countn Activities

Cooperative cancer research programs under
formal government-to-government treaties and
other forms of bilateral agreement constitute a
major segment of the international activities of
the NCI. The first of these cooperative cancer
research agreements was established May 23,
1972, with the signing of the U.S.-U.S.S.R.
Agreement for Cooperation in the Fields of
Medical Science and Public Health. Subse-
quently, additional bilateral programs were
formalized between the NCI and the Japanese

Societ)- for trie Promotion of Science (197ft); the c: I'zz'—z.-.z-

Institute of Oncology, Warsaw, Poland (197^), ce.e.:;--e-:

under the U^.-Polish People's Republic Agree- esr:e-c.i.. :-:

m«it; in 1975 with INSERM, under ar. earlier -~f.zi- -..-z

NIH agreement with LNSERM; the Cairo Career ca-c-.-es a.-c :

Institute (1976), under the aegis of the agree- c:ag-:s.s- s:=.;

ment between the L'ritec States a-t t-.e Ara:: e$:t"a.ze=.. l*:
Republic of Egypt; the '.'.l-.str. :: Sc.er.-ce ar.c

Technology of the Fecera. -et-olic of Ger-r.any • "-: :.-t rese

(1976); the Ca--e- :-st.:.:e Hospital), Chinese a res..: t: .

Academy of ''ec.ta. 5:.e-ces, under the U.S.- .31'.. z^.-^^-

P.R.C. Accorc for CccDeratic- Ir Scierce ar.c a-t '..s c:.-=:

Technology (1979); tre'sCI c: V.i-ar. a-.c t-.e l-s:.:.:e -zr,

Institute of Oncolog>- zi C-e-.oa^ Italy ilSiZ}-. ar.c bioc.--r-.ta. t:

the National Institute of Crcclcsv, Bucat^est, live.- ta-:.-:z

Hungary (1981). ' e::et:s :: ta":

The following sect:t-s test-.te NCI ci^atera.
activities and the prcgress :-at ras oeer. ~.ace • -- et.tr-.:.

through these cooperative efforts. f-:- fr ce. .

Z. .i.

China -a. Ia-:e- ;-5:.:-:r :a-t.;.ta:r: .- a 1-

wee.< N i; -:-•$■:: r-:.:.ec £p-ce— .:.:;•

Bera.'een ranuar>" 1, i9Sl. arc Cctcce.- 31. of T Ce,. _--;-:-as t- z Lr_xe— .las, -s a

1982, seven American scientists visitec ^-.stl- result cf t-esa tztzti, a ~._tlc.s-cl-

tutes in Chma to hold cc~s-lt = tlc-.s. tc p-ese-t plLnary researc" f: e:: .s .-te- t:-:.ter-

lectures, to provide tec---:.:z;- ce- :-s:-a:.:-5, ation for imple- e-:a:.;-, ;e-t.-z -ert.:: ;:

a-t. gsneraliy, to enhance tne exc-a-ge :: :a:a sc~e accltlc.-a. cata frcf. tne ~--_-as-e s.ce.
a-c .--Jior-nation on cancer researc" ::p.t: ::
mutual interest and benefit. Reclprcca^iv, seven • .-. cc-fa:: ::.- -ea!. :...:,. 5:.:.e$ ::r Ic-

stucy/research progra~s a-.c 5:. = -:.:.: -:.-<- Z'-'t "as trf -agct.atet z^'.-ir:- :-e NCI

shops at tn« NCI anc other .-.— er.ca- cancer anc tne Ca,-car l-;t.t_:e -:5:.:a. .- =r.-

centers. Tnese exchanges have effectively f_r- -L-g. ~-e -esea.-cn act.v.:.e; :: re ::-:-::r:

thered the development and l.~.pie~e-: = tlcn cf 1- Z-^-a .-:..:a; a -.:.■.:.:- .-:e.- ■ e-:.:-

joint research activities on cancer p-:c.r — 5 :f tr.a- a'c case-cc-t::. st.C; :: escfagaa.

mutual interest, with a n^ntber of :-a--a.5 :: cancer 1*. LL-.x.a-., a caia-ccn:-:. st.:- of

communication and a variety of — ec-an^s-ns Ln lung :a-:

use. stwC ::

- N - :

jjng, w.t- 5.:se:-a-: a cas.:- :: :.-

Coliabcratior, 'jnder .ArLnex Two of the Health areas cf .■_£■ .-cca'ca a.--c -crta—tj _".

Protocol .— ?_r5_a-t tc tne prcv:s.cns cf .-.--ex Chi-.a.

Two, the NCI recelvec r- c ec.ce—.ic.ogists, eacn

for 1 year of st.cy ressa-c".. .-. t-irc Cnl-ese • .An c-tgrc-n- cf sc.a-:.:.c axc.-an.ges c_r..ng

specialist, an enccsccp.s: c.ag- :::.c.a-. ca-a a .ate .fS. a-c -.c-.-il ■visit by an NCI-

for 1 year of observation a-c e.\par.a-ce .- :-e rrr-sr-ec -_:-.:.:-.:: r.rc-e—lr: --a^ a

clinics and laboratories of se.ectac -~e-.z = ~. zzzz^i. :: 5:.: -.-e aila:: :: :.a:ar>-

cancer centers. sa.e-^.- a-: ::-a- vara a.a-a-ts c" ca--

The Cancer Instirote (Hcsp.ta. , ra. .-g, - ai
the coordinating focus for the activities of two
NCI scientists, each for i .month of exc-a-ges,
relating to the subject of early detect.:- a-c
diagnosis of cancer.

; A ^ - —

Direct Interinstitute coUaboratlo-n (o-tslde of bot-

the Annex) .— T-Is apprcac-- e-cT-7ec cv t-e — e-.t
Progra— CocrcLnatcrs. nas per— .::ac acc.:.:-a^

scientific excnanges and project ca-a.cc — e-t. 2_rl-.g

*^ — A2

• Two .^n-.erica- specialists in anticancer cr_g nese sc.5-:.s:5 ::■ ;:-:■ -asaa-;- .- ~:.a:_.ar

develoD~.ent and evaluatio-. c-e f'c~ fa clclct'. c._--ca. .ar:"a:c'- ic.a-ca, z~ z Zss-c^r

NCI anc one from th a '■'.:-- -a". ca- Ca-car cetac:.:" a-c :.ac-:;-5. .-.ace-;:!.. . :-e NCI

Ce-ta' 1- Ka-sas, \'. sitae C-.-asa ca"cer - „. sa-c 5C-.a-t.;t5 ■; : T-.-a ::" : ;..accratlve

anc p -a"~acewt.cai Lnst-t^tas fcr exc~a-.£a st-c.as re.latec tc aa.-.- ca'.act.:- a"c cias.nosis

and to epidemiologic research. Areas considered
o be of significance and mutual benefit include
identification and characterization of biochem-
ical/biologic markers of tumors, unified concepts
for the collection and analysis of epidemiologic
data, photoimaging and intensification in de-
tection/diagnosis, exploitation of the utility of
photoradiation therapy, and studies related to
genetic predisposition or susceptibility to cancer.
The joint research efforts initiated as direct
interinstitute activities will continue. Other such
initiatives will be considered on a research pri-
ority basis, for instance, studies on automated
cytology and dietary factors and their role in
carcinogenesis and/or in cancer chemopreven-
tion /intervention.

Egypt

The Cairo Cancer Institute, a well-organized
facility, has an accrual of patients with bladder
cancer perhaps greater than that of any other
single institution in the world. Recently, a Phase
II study of chemotherapeutic agents for bladder
cancer was completed, having been initiated in
1976. Twelve drugs were studied in about WO
patients with squamous and transitional cell
bilharzial bladder carcinoma. The preparations
studied included hexamethylmelamine, VM26,
methotrexate, bleomycin, adriamycin, platinum,
Cytoxan, fluorouracil, trenimone, m-AMSA,
vincristine, and pentamethylmelamine. Notable
response rates were 38 percent for hexamethyl-
melamine, W percent for pentamethylmelamine,
^'t percent for vincristine, and 60 percent for
trenimone. The response rates for Cytoxan,
fluorouracil, and DDP are, respectively, 28 per-
cent, 15 percent, and 13 percent.

On the basis of these results, an active chem-
otherapy combination might include vincristine,
pentamethylmelamine, and fluorouracil. The
durable response rate after radical cystectomy
in bilharzial bladder carcinoma is 35 percent
(5-year disease-free survival), not improved by
pre- or postoperative radiotherapy. The com-
bination described above is under active con-
sideration as are other combinations of drugs. It
is anticipated that 100 patients can be entered
on each arm of a two-armed randomized study
within 2 years. The drugs would be made avail-
able by the NCI for this latest study under the
U.S. -Egyptian program.

France

Two broad areas of cancer research now con-
stitute the cooperative activities between
American and French cancer specialists. These
are a basic cancer research program area and a
clinical cancer research program area. Activities
constituting the basic area include biologic and
chemical carcinogenesis, cellular and molecular
biology, viral oncology, cancer immunology, and

hormone research related to cancer. In March
1982, during a review and evaluation meeting,
American and French collaborators agreed to
continue the research programs that have been
established and show promise as well as to stim-
ulate new ideas and support the exchange of
scientists for information and active research
collaboration. Thus, five American investigators
subsequently spent periods ranging from 2 weeks
to 6 months in French laboratories for collabo-
rative studies in hormone and receptor research,
nucleic acid metabolism and alteration, muta-
genesis, and carcinogenesis. Reciprocally, four
French investigators worked in American lab-
oratories on research problems related to gene
expression, hepatitis virus antigens, viral on-
cology, and antiviral interventions in certain
types of cancers.

In Paris, in June 1982, the joint American-
French Committee for Clinical Cancer Research
met to review the progress that had been made
in that area as well as to plan the program for
the subsequent year. They assessed cooperative
research endeavors in the clinical study of breast
cancer treatment, the treatment of osteosar-
coma, biochemical and clinical pharmacology,
and hormone therapy used in breast cancer. An
American epidemiologist spent 6 months col-
laborating with French investigators on biosta-
tistics and clinical epidemiology. An American
endocrinologist spent 2 weeks in France con-
ferring with experts on the biochemical effects
of estrogens in endometrial cancer, while a
French pharmacologist came to the United
States to receive advanced training in biochem-
ical pharmacology so that he could establish a
collaborative research program with his Ameri-
can colleagues upon his return to France.

Federal Republic of Germany

In the environmental carcinogenesis program
area, an epidemiologist from the German Cancer
Research Center in Heidelberg visited the NCI
to exchange information on analytic epidemiol-
ogy and to engage in a case control study of
occupational epidemiology related to workers in
certain hazardous occupations. He was able to
accrue experience in the conceptual aspects of
epidemiologic investigations, data analysis, and
the implementation of studies in the network of
surveillance and monitoring. Based on his ex-
changes in the United States, at the NCI and
New York University Medical Center, he and his
German colleagues are involved with American
counterparts in the development of joint epi-
demiologic studies of workers in the chemical
industry. Included in the joint effort will be the
establishment of a system for cancer registry.

A German pathologist came to the NCI to
conduct joint studies aimed at developing a
common system of classification and terminol-
ogy related to experimental cancers and tumors

so that a comparable system could be established
in the NCI and the German Cancer Research
Center in Heidelberg. Thus, an exchange of
materials and specimens for comparative studies
between the Federal Republic of Germany and
the United States will now be possible.

Hungary

Three American immunologists visited Buda-
pest to attend a course, "Highlights in Modern
Immunology," sponsored by WHO and the Hun-
garian Society of Immunology. The course, con-
sisting of lectures delivered by members of the
Hungarian Society and other internationally
renowned scientists, addressed topics relevant to
immunogenetics, immune receptors, effector
functions and their regulation, and differenti-
ation. The lectures were aimed at young scien-
tists and were, therefore, broad in nature. The
consensus of the Americans was that, in general,
the Hungarian immunologists with whom they
Interacted were impressive and that these Hun-
garian scientists appeared to be very eager to
continue and to further expand the scientific
exchange of information with Americans.

An intramural NCI scientist spent 2 weeks in
Budapest participating in exchanges of infor-
mation on theoretical and practical concepts in
pathology and cancer data processing. As well,
he hoped to determine if the methods of pathol-
ogy data processing used in Hungary have ap-
plication in the United States.

An experimental chemotherapist from the
National Institute of Oncology, Budapest, spent 6
months in the NCI Laboratory of Medicinal
Chemistry and Biology engaging in studies de-
signed to investigate the resistance of murine
tumor cells to alkylating agents used as anti-
cancer drugs. Her work and that of her NCI
colleagues have confirmed the role of the tri-
peptide glutathione in resistance of tumor cells
to alkylating agents. These studies have demon-
strated that it is possible to sensitize the re-
sistant cancer cell completely to the cytotoxic
effects of an anticancer drug such as L-phenyl-
alanine mustard, commercially known as Mel-
phalan. Melphalan is one of the effective drugs,
used in combination with others, for the treat-
ment of breast cancer. Additionally, the chemo-
therapist devoted considerable effort toward the
development of amino acid specific, synthetic-
pelleted diets for use in these experiments. She
contributed significantly to the evaluation of an
Alzet osmotic minipump for continuous intra-
peritoneal infusion of agents such as buthionine
sulfoxime (an inhibitor of glutathionine biosyn-
thesis) and anticancer agents, thus affording a
concentrating effect of antitumor agent at the
site of the cancer.

A transplantation biologist/tumor immunolo-
gist from the National Institute of Hematology
and Blood Transfusion, Budapest, spent 't months

in the Sidney Farber Cancer Institute (SFCI). He
devoted his efforts there to joint research on
developing monoclonal antibodies active against
T cells and monocytes in endothelial cells (EC).
His approach was to collect endothelial cells
from the umbilical cord and to enmass the an-
tigens acting against the monoclonal antibodies.
Based on his research, he concluded that EC are
rich in their expression of HLA-A, B, and C
antigens but that their expression of HLA-DR is
anomalous. EC also share myelomonocytic sur-
face antigens, My-7, Mo-3, and Mo-^. The rele-
vance of these findings to transplantation is
enhanced by initial observations that Mo-'^ is
also expressed in human kidney endothelium as
shown by immunoperoxidase reactions. The re-
searcher became acquainted with the method for
phenotyping leukemic cells by means of mono-
clonal antibodies and, by virtue of an SFCI gift
of a series of monoclonal antibodies, he has
begun phenotyping leukemias and lymphomas in
his laboratory in Budapest. Because of the SFCI
interest in the Hungarian study on HLA-antigen
distribution in gypsies and in the incidence of
various diseases in this ethnic group, the Hun-
garian scientist has provided SFCI scientists with
more than 30 blood samples of Hungarian gypsies
for typing the complement phenotypes.

An experimental pathologist/chemotherapist
from the Semmelweis Medical University in
Budapest spent 6 months at the Roswell Park
Memorial Institute to study methods of tumor
disaggregation—mechanical and enzymic — to
yield single cancer cell suspensions. At the same
time, he developed cell separation methodologies
for biochemical, biologic, and morphologic
characterization of the various tumor subsets
derived from the human tumor cell suspensions.
The subsets, then, were tested for their sensi-
tivity to anticancer drugs. Among 17 tumor cell
types studied, there were significant differences
in the number of cells obtained by disaggrega-
tion. In six cell fractions, intracellular concen-
tration of the anticancer agent, Ara-C, and
-^H-thymidine was higher in the fractions
containing more viable cells. The effect with a
platinum-derived drug was the opposite, in that
results suggest an intensive binding to nonviable
cells.

Italy

Activities in cancer therapeutics and cancer
prevention constitute the efforts of collabo-
ration between American and Italian cancer
specialists.

During the annual review meeting for the
cancer therapeutics program, held in Bethesda,
Maryland, in November 1981, there was a de-
tailed exchange of information in the areas of
clinical trials, basic and clinical pharmacology,
and cancer related epidemiology. Until now, the
need to establish a foundation for a collaborative

project in bicx:hemical pharmacology, breast
cancer treatnnent, pediatric oncology, cancer
naetastases, clinical trials with anthracyclines,
radiation oncology, and biologic response modi-
fiers has motivated the joint workshops and
symposia. In the next year, it is anticipated that
specific joint projects in clinical and preclinical
cancer research will be defined.

Two American pharmacologists from the Ros-
well Park Memorial Institute visited Italian
research centers to discuss and plan collabora-
tive research on the study of modal systems for
investigating drug metabolism and to obtain the
most recent information on the anthracycline
drugs being tested and used in Italy.

From the Italian side, a pediatric oncologist
observed the methods of treatment for childhood
cancer in cancer centers of the United States.
Another pediatrician spent 2 months at the NCI
to participate in a study of Phase I and II drugs
being used to treat solid tumors and acute lym-
phoblastic leukemia in children. He was also a
benefactor of the latest information on dose-
limiting toxicity and antitumor activity of those
drugs being used currently to treat bone sar-
comas, neuroblastoma, and other childhood can-
cers. An immunologist from Italy spent 2 months
at the Frederick Cancer Research Facility to
study the utility and physiologic effects of bio-
logic response modifiers currently in use to treat
cancer. Advanced training in biochemical phar-
macology and experimental chemotherapy was
the goal of a young Italian oncologist who spent
1 year of study /research at the Roswell Park
Memorial Institute in Buffalo, New York.

The annual review meeting for the cancer
prevention program took place in conjunction
with the "Workshop on Leather, Benzene, and
Shipyard Workers," which was convened in Por-
tofino, Italy, in 1981. The workshop was devoted
to discussions on the development of collabo-
rative studies for identification of environmental
determinants of specific cancers. Unique op-
portunities exist in Italy to assess the impact of
certain occupational exposures, particularly
benzene, chromates, and dusts in the leather and
shoemaking industries. Attention was focused, as
well, on the risk of lung cancer among shipyard
workers.

An Italian viral oncologist spent more than a
year at the Mount Sinai Medical School in New
York to study the relationships between polya-
mine biosynthesis and differentiation in an at-
tempt to elucidate the biologic role of these
compounds in the steps leading to differentiation
of the erythroleukemia cells.

An Italian biochemist spent 3 months at the
M.D. Anderson Hospital and Tumor Institute in
Houston, Texas, to learn techniques for the
detection of alterations in DNA induced by car-
cinogens. As a result of this interaction with his
colleagues, this researcher participated in

devising plans to continue the collaborative
studies initiated on the differential and system-
atic enzymatic digestion of DNA and on the sep-
aration and analysis of the subsequent DNA
fragments.

3apan

At the outset of the agreement between the
NCI and the Japanese Society for the Promotion
of Science, 11 specialty areas in cancer research
were pursued jointly. Three years ago, these
were categorized into four broad program areas,
namely, etiology, cancer biology and diagnosis,
cancer treatment, and interdisciplinary research.

Cancer epidemiology, chemical carcinogen-
esis, viral and biologic carcinogenesis, and mo-
lecular biology constitute the principal areas of
research being pursued under the etiology pro-
gram. The principal objectives are to clarify the
cause of human cancers and to determine the
mechanism(s) of carcinogenesis.

During the course of a seminar entitled "Car-
cinogenesis and Gene Expression in Liver Cell
Cultures," held in Hawaii in November 1981,
information was exchanged on the patterns of
expression of various genes during carcinogen-
esis, especially hepatocarcinogenesis. Data pre-
sented at the seminar indicated that changes in
the expression of various genes were reflected
by the production of enzyme systems and other
proteins that were not found in the normal liver
celL The change is so pleiotropic that the mech-
anisms of some of these changes would be in-
trinsically relevant to the carcinogenic process.

Many aspects of intestinal metaplasia were
considered during a conference titled "Intestinal
Metaplasia and Stomach Cancer," convened in
Shimodu, Japan, in March 1982. New histologic
and biochemical enzymatic techniques were
considered as were new methods for histochem-
ical and immunologic assays. An interesting
finding emerged with bearing on the relationship
between mesenchymal and epithelial tissue,
namely, that stroma can influence and guide the
development of epithelial tissues. Although there
was no consensus on whether intestinal meta-
plasia is a precursor lesion for stomach cancer or
only an associated condition, some investigators
believed that a definite precursor relationship
could be demonstrated. Since the cause of
stomach cancer is complex, it is reasonable to
expect that some stomach cancers can be form-
ed by a process not related to the formation of
intestinal metaplasia.

A conference entitled "Cell Interaction and
Cancer," held in Kyoto, Japan, in November
1981, was one of the focal activities in the can-
cer biology program area. Information was
exchanged between American and Japanese
counterparts on a diverse series of topics ranging
from cell-to-cell adhesion in primitive cell

systems to studies of the pathology and biology
of human cancer cells. Highlighting the discus-
sions was the study of differentiation of tissue
mast cells and the growth of leukemia cells in
microenvironments; cell-binding sites of colla-
gen, heparin, and other macromolecules; and
regulatory proteins on transformed cells.

In another activity in this program area Amer-
ican and Japanese immunologists convened a
meeting in Boston in November 1981 on the
analysis of mechanisms for induction of tumor-
specific immunity and experimental approaches
to tumor immunoprophylaxis and therapy. The
participants focused their attention on the anti-
genic nature of tumor cells, expression and reg-
ulations of tumor antigens, fundamental immu-
nologic processes in host response to tumors, and
preclinical applications of tumor immunology.

Hakoni, Japan, was the site in March 1982 of a
meeting on the application of cytology automa-
tion in cancer cytology and cell biology, as a
component of the cancer diagnosis program area.
American and Japanese investigators discussed
the latest information on instrumentation and
data analysis, the application of automated
cytology technology in cell biology, a new tech-
nologic approach for sample preparation, and the
application of automated cytology in cancer
detection.

It was a particularly active year in the cancer
treatment program area in which three meetings
were convened. The first, the Seventh Annual
Program Review Meeting, related to develop-
ment and evaluation of treatment of cancer with
combined modalities of therapy. The conferees
were concerned with three topics: treatment of
oat cell carcinoma of the lung in the United
States and Japcin; development of new method-
ology in clinical and preclinical investigations,
including the progress of human tumor cloning
assay as a predictor for the sensitivity in situ of
human tumors to administered drugs; and new
antitumor agents, natural and synthetic, now in
Phase I and II as well as those still in preclinical
stages of development.

The second assembly in this program, which
took place in October 1981 in Maui, Hawaii, was
the first meeting on preclinical and clinical
trials of tumor immunology. Subjects for infor-
mation exchange included experimental studies
of cancer immunotherapy, possible application of
human T cell hybridomas for immunotherapy of
cancer, monoclonal antibody therapy in man,
adjuvant immunotherapy of lung cancer with
bacterial cell wall skeleton preparations, current
status of interferon therapy, and clinical trials
using immunotherapeutic approaches.

The third meeting, held in Tokyo in November
1981, concerned advances in the treatment of
bladder cancer. Topics for information exchange
were superficial cancer of the bladder, deeply
invasive cancer of the bladder, metastatic

disease, prevention of bladder cancer, conduct of
clinical trials, and projected cooperative bladder
cancer treatment programs. In general, the
exchanges served as a foundation for further
cooperative studies of bladder cancer as well as
basic and clinical investigations on bladder can-
cer. In addition, criteria for diagnosis and for
development of protocols were established,
which will be useful to investigators in both
countries for facilitating the mutual under-
standing and use of diagnostic, therapeutic, and
clinical technologies.

In Hawaii, in March 1982, a seminar entitled
"Neural Crest Tumors" represented a key ac-
tivity in the interdisciplinary program area.
During the session, attention centered on certain
syndromes associated with tumors or familial
neoplasia derived from the neural crest and on
differences between the frequencies of these
tumors in both countries.

American and Japanese viral oncologists,
pathologists, and epidemiologists assembled in
Seattle, Washington, in March 1982 to discuss
the nature of T cell leukemias and their probable
etiologic agents. During this symposium entitled
"T Cell Leukemia/Lymphoma—Role of Human
Type C Retroviruses," it was learned that teams
of American and Japanese virologists had inde-
pendently isolated and identified retroviruses
associated with HTLV and ATLV, respectively.
These newly identified human retroviruses seem
to be identical or very similar to each other. The
viruses are closely associated with mycosis
fungoides, Sezary syndrome, and adult T cell
leukemia that belong to the category of dif-
ferentiated T cell lymphoma and leukemia. The
viruses have been found to be endemic in the
southwestern part of Japan and in certain Car-
ibbean islands.

Related to the foregoing, an American path-
ologist visited several Japanese laboratories to
review information and to plan cooperative
studies on leukemias and lymphomas. Recipro-
cally, a Japanese scientist came to the United
States to visit cancer centers for the study of
the classification of lymphomas. Another Jap-
anese, an immunologist, spent his time studying
methods for jn vitro sensitization and testing of
cytotoxic lymphocytes.

Poland

Exchange of scientists between the Polish
People's Republic and the United States has
continued to be effective, despite the current
political climate in Poland.

An American pharmaceutical chemist spent 6
weeks at the Institute of Oncology in Warsaw to
conduct collaborative studies in nuclear medi-
cine and radiopharmaceutical research. With his
Polish counterpart, he investigated the possi-
bilities of using microspheres as carriers of

radioactive isotopes for treating certain types of
cancers such as hepatic carcinoma. The experi-
ments demonstrated the stability of microsphere
carriers in animal models as well as the potential
for the use of such agents in treating cancers in
humans.

During the year, six Polish scientists visited
the United States to do research in their spe-
cialties. The first, a tumor biologist, visited
centers of excellence in the United States to
exchange information and learn of recent ad-
vances in radiation biology, cancer immunology,
and biology. A biologist from the Institute of
Oncology in Warsaw spent 6 months collabora-
ting on DNA polymerase research at the Roche
Institute of Molecular Biology. A Polish bio-
chemist came to do research on chemical car-
cinogenesis. A pharmacologist spent his time in
collaborative studies of biochemical pharmacol-
ogy and tumor immunology at the Roswell Park
Memorial Institute.

The director of the Institute of Oncology in
Warsaw, after attending the 13th International
Cancer Congress in Seattle, Washington, visited
cancer centers in that area, as well as others in
the United States, for discussions on the progress
and achievements of the Polish National Cancer
Program as well as the accomplishments under
the U.S. -Polish People's Republic Cooperative
Cancer Program. Finally, a pediatrican from the
Nation Research Institute of Mother and Child in
Warsaw observed and studied treatment modal-
ities and procedures for childhood cancer in the
Pediatric Oncology Branch of the NCI.

U.S.S.R.

The six original program areas ~ in effect
since inception of the U.S.-U.S.S.R. Health
Agreement in 1972 ~ were modified, restruc-
tured, and/or merged during the Sixth U.S.-
U.S.S.R. Meeting on the Problem of Malignant
Neoplasia, held in Bethesda, Maryland, Septem-
ber 1981. Thus, the scientific areas of cancer
treatment, carcinogenesis, and cancer preven-
tion now constitute priority areas for continuing
collaboration between American and Soviet
cancer specialists.

An NCI intramural scientist, during his No-
vember 1981 visit to Moscow's AU-Union Onco-
logic Scientific Center, was able to engage in
productive discussions on cancer chemotherapy,
especially from the view of detailed analyses of
raw data and participation in clinical rounds for
the observation of Soviet patients entered into a
parallel study of tamoxifen as an adjuvant in the
surgical treatment of breast cancer. Preliminary
data indicate positive treatment results with this
agent, and the patient accrual under the study
should yield promising information regarding this
mode of treatment. The NCI provides the ta-
moxifen and research counsel for this parallel
study.

The NCI has been provided with additional
quantities of the Soviet drug known as histar, for
completion of preclinical testing in xenograft
systems following demonstration of positive
histar activity in L-1210 leukemia, B-16 mela-
noma, and CD8f mammary tumor. The Soviets
are also preparing samples for NCI testing of
three compounds of natural origin and their
indication of potential use as anticancer agents.
These are bacuchiol, an antibiotic, and chrys-
ophanol and cynodontin, which are lichen
products.

During their January-February 1982 visit to
the NCI and other U.S. cancer centers, two
Soviet chemotherapists joined American col-
leagues at the University of Maryland Cancer
Center to design and develop a protocol for a
"Phase I Clinical and Pharmacologic Trial of
Platinum diammine (1,1-cyclobutane-dichlor-
oxyIate)2-(-0,0')." The agent is commonly re-
ferred to as CBDCA. Paralleling the study of the
American scientists and clinicians, the Soviets
will pursue (1) establishing the maximum human
tolerable dose of CBDCA; (2) evaluating its
toxicity in patients with previously treated and
untreated malignancies; and (3) researching its
antitumor activity and its clinical pharmacoki-
netics. The pharmacologic committee of the
U.S.S.R. Ministry of Public Health approved the
use in Soviet patients of CBDCA, which has been
provided to the U.S.S.R. scientists by the NCI.
Evaluation of the protocol is underway in the
U.S.S.R. as well as in the United States.

From May 23 to June 6, 1982, a medicinal
chemist from the University of Michigan was in
the U.S.S.R. to participate in a meeting on drug
design and bioorganic chemistry as well as to
meet with colleagues in a variety of institutes
for discussion of drug development and design,
advances in bioorganic chemistry, and organic
and medicinal chemistry. He returned with
abundant information from Soviet colleagues on
progress they have made with a number of
alkylating anticancer compounds as well as
adamantane derivatives, some vinca compounds,
and glycopeptide preparations such as the Soviet
agent known as khanerol.

A microbiologist from Pennsylvania State
University spent 2 months in the U.S.S.R. pur-
suing joint experiments on "Herpesvirus Papio:
Modulation of Virus Expression in Baboon Lym-
phoma" at the Institute of Experimental Path-
ology and Therapy, Sukhumi, Georgian S.S.R. The
Sukhumi Center is perhaps the largest facility in
the world for primates in captivity. In general,
the scientific benefit to American scientists is
accessibility to this large colony of baboons and
other primates. These animals have been a val-
uable resource for isolating primate retroviruses,
isolating primate herpesviruses and determining
their role in the development of certain lympho-
proliferative diseases, and identifying genetic
factors resulting from inbreeding.

After their participation in the 13th Interna-
tional Cancer Congress in Seattle, Washington,
two Soviet chemotherapists spent an additional 3
weeks in the United States visiting centers of
excellence related to the studies they are pur-
suing jointly or independently. Their exchange of
information and their interactions with Ameri-
can colleagues related to problems of the bio-
chemical pharmacology of anticancer agents, the
design and development of potentially useful
anticancer compounds, and the preclinical
testing of such agents for their toxicity and
efficacy in animal tumor systems.

Meetings of American-Soviet working groups
in the program areas of carcinogenesis and can-
cer prevention will be convened in Moscow in
early 1983. Prime consideration will be given to
developing work plans for research activities of
mutual interest and benefit to cancer patients in
both nations.

The spectrum of cooperative cancer research
activities, under bilateral agreements between
the NCI and cancer institutes of nine nations, is
illustrated in Table ^-l.

Table ^--2 indicates that a total of 236 scien-
tists~96 from the United States and IkO from
nine foreign nations— participated in collabo-
rative cancer research activities under the aus-

pices of bilateral agreements. More than a third
of the total number of scientists spent their
sojourns away from home engaging in one-on-
one, scientist-to-scientist interactions for col-
laborative research. Almost a third of the total
scientist exchangees pursued activities related
to cancer treatment, drug design and develop-
ment, and preclinical evaluation of potentially
useful drugs. Pathology, early detection and
diagnosis, biochemistry and molecular biology,
and epidemiology followed as scientific areas of
high interest and relevance.

International Cancer Research Data Bank Program

Established by the National Cancer Act of
1971, the International Cancer Research Data
Bank (ICRDB) Program has developed into an
effective, multifaceted system for the rapid
exchange of results from cancer research by the
international team of scientists and clinicians.
This comprehensive, international resource for
cancer information provides a unique service to
cancer researchers almost everywhere in the
world. To facilitate the transfer of available

Table 'J- 1.— Cooperative cancer research under bilateral agreements

Cancer
research area

F.R.
China Egypt France Germany Hungary Italy 3apan Poland U.S.S.R.

Treatment

Drug development
and testing

Immunology

Virology

Genetics

Epidemiology

Control and
education

Diagnosis and
detection

Pathomorphology

Autocytology

Carcinogenesis

Prevention

Biochemistry

Radiation biology

E
E

E = in effect

N = in negotiation

T = information exchanges and training
35

cancer research data, the ICRDB Program has:
(1) established three online computer data bases
constituting the CANCERLINE System, which
enables scientists to retrieve cancer information
easily at more than 3,000 locations within the
United States and in 13 other countries; (2) de-
veloped a series of publications providing com-
plete coverage of cancer research information,
in special formats designed for easy use and
quick reference; and (3) supported a variety of
specialized information collection, analysis, and
dissemination activities.

The Computer Databases of the
CANCERLINE System

The three data bases constituting the CAN-
CERLINE System are CANCERLIT (cancer lit-
erature), CANCERPR03 (cancer research proj-
ects), and CLINPROT (clinical protocols).

CANCERLIT contains nearly 325,000 sub-
stantive abstracts of information accumulated
from published scientific papers and from those
presented at meetings, symposia, and confer-
ences; books; technical reports; and research
theses. CANCERLIT is growing at an annual rate
of nearly ^5,000 abstracts, selected from over
2,000 biomedical journals. Because of stringent

input processing requirements and monthly up-
dating of the CANCERLIT data base, the most
recently published research results are quickly
available to cancer researchers worldwide. Since
early 1980, all new literature entries have been
indexed with the Medical Subject Heading vo-
cabulary developed by the National Library of
Medicine, making retrieval easier during online
searching. Ten percent of the accessing of CAN-
CERLIT is conducted by foreign scientists and
institutions. Activities related to screening,
indexing, and abstracting cancer-related liter-
ature are performed for the ICRDB Program
under contract.

Descriptions of some 20,000 current cancer
research projects in 83 countries are the ele-
ments of the CANCERPROa data base, the most
comprehensive source available for ongoing
cancer project information. Included in this data
base are some 5,000 foreign project descriptions
collected by an international network of data
input coordinators. Collection, input, and quar-
terly updating of the project descriptions in
CANCERPROJ are performed by a contractor-
operated Current Cancer Research Project
Analysis Center. The CANCERPR03 connect
hours by user type for the first half of FY 1982
were 216.39.

Table 'f-2.~The exchange of scientists under NCI's bilateral agreements programs

Area of specialty

Collaborating

Number scientists
to . . .

00
Number scientists E ^
from ... " g

For Individual g §•
meetings exchanges £ "^

ij Q

Detection <5c
Diagnosis

u
U

Biochemistry &
Molecular Biology

c
o

u
■♦->
3

c
_o

c
>

!2
£
•o
■q.

country

For Individual
meetings exchanges

o
a,

China

3 1

Egypt

France

Germany

(F.R.)

Hungary

Italy

Japan

Poland

U.S.S.R.

Totals

en-

31 1

Summaries of nearly 3,500 experimental can-
cer therapy protocols are the substance of
CLINPROT, the data base providing worldwide
access to information on new procedures, agents,
and combinations of modalities/agents under
evaluation for treating cancer patients in major
American and foreign cancer centers. Of these
protocols, 1,500 are clinically active while the
remainder serve as a unique reference source.
Collection and input of protocol summaries and
quarterly updating of CLINPROT are functions
performed by domestic and international con-
tractors. The connect hours for CLINPROT
during the first half of FY 1982 were 1^9.03.

The information contained in the data bases of
CANCERLINE is available through the compu-
terized biomedical information network of the
National Library of Medicine.

Special Information Activities of
the ICRDB Program

Under contracts with the NCI, three Cancer
Information Dissemination and Analysis Centers
(CIDAC's) function as information resources in
three broad areas of cancer research: the CIDAC
for Diagnosis and Therapy, University of Texas
System Cancer Center, and M.D. Anderson Hos-
pital and Tumor Institute, Houston; and the
CIDAC for Carcinogenesis and for Cancer Vi-
rology, Immunology, and Biology, both at the
Franklin Research Center, Philadelphia. Each
CIDAC is staffed by scientists and served by a
consultant network with special expertise ap-
propriate to the fields pertinent to each CIDAC.
Within its own subject area, each CIDAC pre-
pares Cancergrams and Oncology Overviews ,
performs custom CANCERLINE searches, and
provides scientific guidance to the ICRDB
Program.

The Clearinghouse for Ongoing Research in
Cancer Epidemiology is a cooperative project
sponsored jointly by the ICRDB Program, lARC
in Lyon, France, and the German Cancer Re-
search Center in Heidelberg. The clearinghouse,
located in Lyon, collects, processes, and dis-
seminates detailed data on research related to
cancer epidemiology and studies of human can-
cer causation in countries throughout the world.
The clearinghouse also prepares lists of epide-
miology researchers and resources, responds to
technical inquiries, and produces an annual
Directory of Ongoing Research in Cancer
Epidemiology .

The Latin American Cancer Research Infor-
mation Project (LACRIP) was developed through
the ICRDB Program in collaboration with the
PAHO and its Regional Library of Medicine in
Sao Paulo, Brazil. LACRIP serves as the source
for identifying, collecting, and supplying Latin
American biomedical literature, summaries of
ongoing cancer-related research projects, and
active therapy protocols in Latin America for

inclusion in the CANCERLINE system. PAHO
also serves as the center for searching ICRDB
data bases and providing documents and data in
response to requests for information from cancer
researchers in Latin America. In addition, an
automatic service that selectively disseminates
information to cancer researchers and clinicians
in Latin America is provided.

Through LACRIP, a series of collaborative
cancer treatment research projects was devel-
oped between 10 cancer centers in the United
States and 12 cancer centers in Latin America.
Although these activities are now supported
completely by the NCI Division of Cancer Treat-
ment, LACRIP maintains the clinical data
gathered at the Latin American centers.
LACRIP also arranges for the exchange of pro-
fessional staff between the American and the
Latin American centers to promote a better
understanding of current cancer treatment
research and modalities of therapy available in
the United States.

In cooperation with the International Union
Against Cancer, the ICRDB Program provides
partial support for a special Committee for
International Collaborative Activities (CICA)
within the framework of the union. One of the
CICA activities is the collection of data on
ongoing cancer research projects, including
clinical protocols, from more than 70 countries.
CICA personnel identify and promote collabo-
rative projects among cancer centers and cancer
scientists in different countries. CICA period-
ically publishes an updated International Direc -
tory of Specialized Cancer Research and Treat -
ment Establishments , which describes more than
700 of the world's cancer centers, their cancer
research and treatment activities, and their
resources. The International Cancer Patient
Data Exchange System (ICPDES) has been es-
tablished as part of the CICA project. Currently,
scientists and clinicians from nine European and
five American cancer centers participate in this
study, which could result in the development and
establishment of the first internationally rec-
ognized and standardized tumor registr>', from
which valuable comparative data would be pro-
vided from a multitude of countries on cancer
epidemiology, treatment, and prevention.

Entries of cancer case data for six different
cancers, from each of the participating centers,
is detailed in table k-2>. The entries for each
cancer site were accumulated from November
1977 through July 1981.

Scientist-to- Scientist Communication

The ICRDB Program, through the International
Union Against Cancer in Geneva, Switzerland,
encourages international scientist-to-scientist
communication through the International Cancer
Research Technology Transfer Program
(ICRETT). The goal of this program is to

Table 'f-S.— Patient data, by cancer site and collaborating institute,
entered into the ICPDES system

Breast

Colon

Rectum

Larynx

Hodgkin's

Non-Hodgkin's

Total

M.D. Anderson

3,119

1,055

548

383

384

„

5,489

Mayo

1,370

922

508

201

181

268

3,450

Memorial

3k7

178

177

1,427

Roswell Park

375

204

106

822

Duke

121

214

Total U.S.

5,932

2,390

1,369

719

685

307

11,402

Amsterdam

619

930

Essen

236

371

Heidelberg

272

484

Milan

1,47^

106

119

184

118

2,001

Moscow

818

151

126

153

—

1,306

Rotterdam

1,519

167

224

110

2,189

Bordeaux

1,149

159

149

140

1,728

Brussels

674

903

Budapest

1,563

239

127

2,080

Total Europe

8,324

482

906

1,060

814

406

11,992

Total ICPDES

14,256

2,872

2,275

1,779

1,499

713

23,394

promote direct and rapid transfer of information
about new or improved technology or methodol-
ogy between two or more investigators, located
in different countries, working on similar re-
search projects. This interaction is accomplished
by the support of short-term visits to conduct
collaborative research projects in a short time,
usually 2 to 4 weeks. Since the inception of the
program in 1975, 586 awards had been granted
through 3uly 1982.

In many instances, these associations between
scientists from different countries developed
into significant collaborative studies that other-
wise might have lacked the necessary impetus
and resources to develop. For instance, a
geneticist from the Department of Tumor Biol-
ogy of the Karolinska Institutet in Stockholm is
pursuing molecular analyses of chromosomal
translocations in cancer. Through the literature,
he learned of a scientist at the Beatson Institute
for Cancer Research in Glasgow, Scotland, who
has sorted out specific chromosomes and iden-
tified their molecular breakpoints. These break-
points led to chromosome translocations asso-
ciated with chronic granulocytic leukemia and
Burkitt's lymphoma. Newly developed techniques
for chromosome sorting by means of the fluor-
escence activated cell sorter (FACS) were used.
Although the Swede had a new FACS available to

him in his own institute, he had had difficulty in
applying the instrument for the analyses he
wished to perform. During a 3-week exchange,
he was able to learn about the features of this
unique apparatus and apply FACS techniques for
chromosome sorting as well as cloning proce-
dures for small amounts of DNA from trans-
located chromosomes. Overall, communication
between the two scientists supported their col-
laborative research.

A biochemist from the Institute of Molecular
Biology in Salzburg, Austria, spent 1 month in
the laboratory of a fellow biochemist at Wash-
ington University, St. Louis, Missouri. Both were
working on collagenase production in human and
animal tumors, recognizing that several human
and animal carcinomas contain collagenase and
release this enzyme in vitro. They perceived, as
well, that the role of collagenase in growth and
invasiveness of tumor has not been explained
precisely. The Austrian was interested in a more
sensitive method to detect small amounts of
collagenase in the supernatant fluid of tumor
cells. He learned of the American biochemist's
modification of the enzyme-linked immunosor-
bent assay, which he believed would meet his
own requirements. During his sojourn with the
American biochemist, the Austrian scientist was
able to master the new technique and return to

his laboratory where he is now studying the de
novo synthesis of coUagenase, the nature of the
latent enzyme, and the source of this enzyme in
human skin carcinoma. The successful collabo-
rative efforts of the two biochemists continue.

A biochemical pathologist from the Yale Uni-
versity School of Medicine had been studying the
phenomenon of epidermal (epithelial) cell move-
ment, which is relevant to the histologic and
pathologic process of wound closure and epi-
thelial cancer cell invasion and metastasis. In
analyzing these processes, he isolated a molecule
from serum that epithelial cells need in order to
move in vitro . This molecule, a glycoprotein
named epibolin, is necessary and sufficient for
epidermal cell movement. In the absence of
serum, no epidermal cell spreading is observed,
and in the presence of epibolin-antibody, serum
does not support epidermal cell spreading. The
purpose of his visit with a colleague at the Uni-
versity of Zurich was to learn what specific role
the spreading protein plays in the movement of
cancer cells, since cancer cell motility is central
to the problem of neoplastic invasion and metas-
tasis. The Swiss scientist, a world-renowned
scholar of cancer cell movement, developed
unique methods for measuring cancer cell mo-
tility. In addition, he developed several squamous
cell carcinoma lines for such studies. By virtue
of his experience in Switzerland, the American
scientist was able to confirm his hypothesis and
his experiments are consonant with the con-
clusion that the glycoprotein epibolin is the
necessary component for in vitro spreading of
cells from human squamous carcinoma.

A radiotherapist/epidemiologist from the John
F. Kennedy Memorial Hospital in Monrovia,
Liberia, journeyed to the NCI of Canada, in
Toronto, where he spent 1 month designing,
constructing, administering, and analyzing
questionnaires for case-control and cohort
studies used in epidemiology. After learning
about questionnaire design, questionnaire meth-
ods, and indepth interviewing, he attended field
studies with several Canadian interviewers to
gain practical insight into problems associated
with interviewing. He learned the procedures for
choosing controls for the various types of case-
control and cohort studies as well as the vali-
dation and sensitivity of testing and final eval-
uation of data. At the end of his stay, he was
able to put together the skeleton of a question-
naire for a case-control study scheduled for
completion in Liberia and tried out first in a
pilot study and later as a multicenter study in
collaboration with his colleagues in Africa.

A surgeon from the Yale University School of
Medicine pursued intense study for 3 weeks with
a surgeon from the University Hospital in Zurich,
from whom he obtained instruction in both sur-
gical anatomy of the cranial base and the actual
operative technique for treatment of tumors
located at the skull base. The principal deter-

minant of patient survival in the treatment of
tumors in this anatomical site involves the abil-
ity to obtain total gross tumor removal before
instituting adjuvant radio- or chemotherapy.
Through actual observation of surgical proce-
dures, video tapes, and the use of the Swiss
surgeon's extensive library, the American sur-
geon obtained a good deal of firsthand, practical
information. This experience enabled him to
perform the Swiss procedure at Yale.

A photochemist from the Agricultural Re-
search Organization in Bet Dagn, Israel, spent 1
month in the Laboratory of Pathophysiology of
the NCI. He wanted to understand the initial
chemical events that follow photoexcitation of
the porphyrin molecule and its subsequent inter-
action with other cell constituents. He was in-
terested in optimizing data for the preferential
uptake and retention by malignant tumors of
porphyrins, which are photochemically active
compounds. Because porphyrins are efficient
photodynamic sensitizers and certain malignant
cells become fully vulnerable to light, he hoped
to learn the mechanism(s) by which tumor cells
are inactivated during exposure to porphyrin and
irradiation.

An English biochemist/physician spent 2 weeks
in the Cancer Treatment and Research Center in
San Antonio, Texas, to study the techniques
currently used to grow colonies of human tumor
cells on soft agar. The visit and exchanges en-
abled him to make small but important modifi-
cations to the techniques currently used in his
laboratory for the culture of ovarian, breast, and
colonic carcinoma. As well, he was able to com-
pare the up-to-date results obtained from cyto-
toxic drug assays in this laboratory using reduc-
tion in colony-forming activity as an end point.
Since his return to South Hampton, England, he
has been able to redefine the objectives of his
present project towards: (1) using an animal
model to see if the in vitro assay can be truly
predictive of in vivo activity of cytotoxic drugs;
and (2) looking more closely at the biology of
colony formation by tumors and to improve the
proportion of growing in vitro.

In summary, table ^-^^ designates the disci-
plinary studies pursued by the 586 ICRETT
awardees, while table ^-5 indicates the inter-
national flavor of the ICRETT Program and the
interaction between scientists from ^7 coun-
tries/areas.

NIH Visiting Program

During 1982, scientists of the NCI received
260 Visiting Scientists, Associates, and Fellows
from ^5 countries who came to the United States
to engage in collaborative cancer research
activities. Five of the visitors were appointed as
Experts and 68 came as Guest Workers, whose
financial support was provided by sources other

Table '^-'^.--International cancer research technology transfer

Disciplines

1976 1980 1981 1982

6 1977 1978 1979 + Apr 81- April/ Total

months 3FM 81 Mar 82 June

Epidemiology, biostatistics, and registries

—

Biochemistry, molecular biology, and
biophysics

l^f

l^t

6'f

Viral carcinogenesis

Chemical carcinogenesis

Cell biology and cell genetics

I'f

Experimental pathology
(including histopathology and cytology)

1^^

«^9

Immunology

—

I2tt

Experimental chemotherapy

Surgery

Clinical chemotherapy and endocrinology

—

Radiobiology and radiotherapy

Controlled therapeutic trials

—

Detection and diagnosis

—

Behavioral and social sciences and the

-^---

relationship to cancer

.--

—

11-

Environmental factors and prevention

—

Totals

102

103

126

139

586

than the NCI. These visiting scientists pursued
their research in the laboratories of the NCI
Divisions of Cancer Treatment, Cancer Cause
and Prevention, and Cancer Biology and Diag-
nosis. These mutually beneficial associations
afforded the NCI host scientists opportunities to
learn from their visitors about cancer problems
in a given foreign country; about factors peculiar
to that nation that might be related to the mor-
bidity and mortality of cancer; and about activ-
ities underway toward the management, treat-
ment, and prevention of cancer. Reciprocally,
the foreign visitors enjoyed unique opportunities
to improve their mastery of the scientific meth-
od or to develop their potential for significant
contributions to basic and /or clinical research.
The value of this scientific interaction is indis-

putable because cancer patients throughout the
world are benefiting from improved care.

Extramural Programs

During 1982, the Divisions of Cancer Treat-
ment (DCT) and Cancer Cause and Prevention
(DCCP) maintained extensions of their program-
matic objectives in foreign countries through 18
contract research activities, compared to 3k
during the previous year and 53 during 1980. No
contractual research was in effect to extend the
research effort of the Division of Cancer Biology
and Diagnosis (DCBD).

The Division of Extramural Activities (DEA)
provided the fiscal support, through 59 grants, to

scientists in foreign institutions conducting basic
and applied cancer research.

Institutions in 17 nations were recipients of
NCI grants and contracts. Thus, the outreach of
NCI support extended to Australia, Belgium,
Canada, Denmark, Finland, France, Ghana,
Israel, Italy, Japan, Korea, South Africa, Swe-
den, Switzerland, Tanzania, Tunisia, and the
United Kingdom.

Division of Cancer Treatment

DCT research contracts have been awarded to
investigators in nine institutions of five foreign
countries for studies related to the characteri-
zation of anticancer agents, the search for po-
tentially useful anticancer agents such as those
of microbial and natural origin, the screening
and testing of such compounds, their biochemical
pharmacology and toxicology, the synthesis of
radiation sensitizing agents, and clinical trials on
specific cancers. One contract is specifically for
the production and delivery of human lympho-
blast interferon. Examples follow of this inter-
national collaborative effort in cancer drug
design and development and in preclinical and
clinical evaluation.

Through its Cancer Chemotherapy Research
Collaborative Office at the Institut Jules Bordet
in Brussels, Belgium, the DCT maintains inter-
action with investigators of European nations
concerning ongoing cancer research programs on
both continents. The Brussels office has been
especially useful in disseminating information on
experimental and clinical pharmacology and
clinical trials and organizing symposia conducted
jointly by American and European investigators.
The Institut Jules Bordet provides a flow of new
agents with potential anticancer activity to the
European pharmaceutical industry.

Under contract, materials collected in nor-
thern Europe are screened against animal tumors
at the Institut Jules Bordet in accordance with
established in vivo protocols. Approximately
11,000 substances that have been identified as
potentially useful anticancer agents are cur-
rently being tested.

Under contract to the NCI, the Institute of
Cancer Research in England is conducting re-
search on design, synthesis, and evaluation of
novel compounds, both nitroimidazoles and other
heterocycles, as potential radiation sensitizers.
Several classes of heterocycles have been syn-
thesized and are in the process of evaluation.
Other activities in the Institute of Cancer Re-
search involve: (1) validation of human tumor
xenografts as models for cancer chemotherapy;
(2) the use of human tumor xenografts and
transplantable mouse tumors for testing new
compounds of interest to the NCI; (3) the toxi-
cology, pharmacology, and initial clinical trials
of new drugs developed in this project; and W
studies of the biochemical basis for treatment

Table 'f-^.—Countries/areas of origin of

ICRETT awardees and their destinations,

1976-82

Origin

Destination

Argentina

Australia

Austria

Belgium

Brazil

Canada

Bulgaria

P.R.C.

Canada

Taiwan

P.R.C.

Colombia

Taiwan

Denmark

Colombia

Finland

Czechoslovakia

France

Denmark

Germany (F.R.)

Egypt

Hungary

Finland

Iceland

France

India

Germany (F.R.)

Israel

Greece

if-

Italy

Hungary

Japan

India

Malaysia

Iran

Mexico

Israel

l^6

Netherlands

Italy

New Zealand

Japan

Norway

Kenya

Peru

Liberia

Poland

Malaysia

Sweden

Mexico

Switzerland

Netherlands

United Kingdom

New Zealand

U.S.A.

258

Nigeria

U.S.S.R.

Norway

Venezuela

Peru

1
1

Philippines

Poland

31 countries/areas

586

South Africa

Spain

Sri Lanka

Sweden

Switzerland

Thailand

Turkey

Uganda

United Kingdom

Uruguay

U.S.A.

135

Yugoslavia

Zambia

1^7 countries/areas

586

Table tt-G.—The NCI-PAHO collaborative cancer treatment research program
by number of protocols and patient accrual

Latin American Center

Protocols USA Cancer Center

Patient
accrual

Grupo Argentine de Tratamiento

de Ids Tumores Solidos (GATTS)
Buenos Aires, ARGENTINA

Grupo Argentine de Tratamiento

de la Leucemia Agunda (GATLA)
Buenos Aires, ARGENTINA

Institute Angel H. Roffo
Buenos Aires, ARGENTINA

Institute Nacienal de Cancer
Rio de Janeiro, BRAZIL

Fundacae A.C. Camarge
Sao Paulo, BRAZIL

Universidad Catelica de Chile
Santiago, CHILE

Institute Nacienal de Cancerologia
Bogota, COLOMBIA

Hospital de Nines "Dr. C.S. Herrera"
San 3ese, COSTA RICA

Hospital San Juan de Dies
San Jose, COSTA RICA

Hospital de Oncolegia
Mexico City, MEXICO

Institute Nacienal

de Enfermedades Neeplasicas
Lima, PERU

Hospital de Clinicas

"Dr. Manuel Quintela"
Montevideo, URUGUAY

Institute de Oncolegia "Luis Razetti"
Caracas, VENEZUELA

13 centers/9 countries

Georgetown University 168

Washington, D.C

Georgetown University 3^1

Washington, D.C.

Georgetown University 15

Washington, D.C.

M.D. Andersen Hospital 137

and Tumor Institute
Houston, TEXAS

Memorial Sloan-Kettering ^^5

Cancer Center
New York, NEW YORK

Wisconsin Clinical Cancer Center IJ^t

Madison, WISCONSIN

Roswell Park Memorial Institute 98

Buffalo, NEW YORK

Baylor University Medical Center (NA)

Dallas, TEXAS

Baylor University Medical Center (NA)

Dallas, TEXAS

New York University Cancer Center it5

New York, NEW YORK

Comprehensive Cancer Center 608

for the State of Florida
Miami, FLORIDA

University of Maryland 109

Cancer Center
Baltimore, MARYLAND

Yale University Medical Center (NA)

New Haven, CONNECTICUT

10 centers IS'fO

NA = newly admitted to CCTRP.

response or failure aimed at the design, syn-
thesis, and detailed evaluation of new drugs.

Under contract, the NCI maintains a Chemo-
therapy Liaison Office in the Japanese Founda-
tion for Cancer Research in Tokyo. The program
is designed to foster close collaboration between
American and Japanese investigators in the
development and application of new clinical
anticancer drugs and in the exchange of pre-
clinical experimental and clinical scientific
knowledge and materials requisite for maximum
progress in cancer therapy.

Scientists at the Mario Negri Institute of
Pharmacologic Research in Milan, Italy, aid the
NCI, under contract, with a multidisciplinary
approach to drug development. The research
tasks include: (I) collection and screening of
antineoplastic agents obtained from southern
Europe; (2) screening of immunochemotherapeu-
tic agents; and (3) pharmacologic studies of new
agents with emphasis on the relationship of
pharmacokinetics with in vivo antitumor effects.

In association with the Muhimbili Medical
Center in Tanzania, the OCT is engaged in a
study of the use of oral 1 3-cis retinoic acid as a
chemopreventive agent of skin cancer in albino
Africans. These people, living in the equatorial
zone, are subject to the most intense ultraviolet
radiation on the surface of the earth and there-
fore to a 100 percent greater probability of skin
cancer.

Five years ago, through the ICRDB Program's
special information activity, LACRIP, collabo-
rative clinical studies were developed among
nine cancer centers in the United States and six
centers in Latin America. This cooperative re-
lationship with Latin American cancer institutes
is now managed by the DCT as the NCI-PAHO
Collaborative Cancer Treatment Research Pro-
gram. Currently, investigators in 13 Latin Amer-
ican cancer institutes/hospitals and in 10 Amer-
ican cancer centers are pursuing joint research
activities. The treatment protocols now in eval-
uation include therapeutic concepts in hemato-
logic malignancies, childhood malignancies,
breast cancer, gynecologic cancer, gastroin-
testinal cancer, and osteosarcomas. Multimodal
concepts in solid tumors are being pursued in
advanced breast and head and neck cancer. Over
the total life of the program as many as 37
therapy protocols have been active in a given
year. Eleven of these protocols have been com-
pleted or terminated, leaving 26 still under ac-
tive investigation. Since the inception of this
multinational effort, 2,3^^2 patients have been
accrued under the various protocols. The col-
laborating cancer centers, the numbers of active
protocols, and patient accrual are listed in table
^-6. Table 't-Z indicates the cancers being stud-
ied in various organ sites.

Personnel of the DCT play key roles in the
NCI bilateral agreements with China, Egypt,
France, the Federal Republic of Germany, Italy,

Japan, and the U.S.S.R. through participation in
clinical trials, preclinical screening and testing
of potentially useful anticancer agents, evalua-
tion of the activity of substances indicating
properties for biologic response modification,
and programs in experimental/development
therapeutics.

Division of Cancer Cause and Prevention

The DCCP maintains active associations with
international organizations and agencies that
have well-defined objectives in cancer research,
especially its cause and prevention. The DCCP is
also engaged in collaborative contract research
in seven institutions or agencies in six foreign
nations. These foreign extensions of the DCCP
research program enable the Division to support
fundamental studies on normal and malignant
cells in relation to such carcinogens as viruses
and chemicals, as well as epidemiologic studies
of human populations for the identification of
risk factors predisposing individuals to various
cancers. Excellent model systems are available
to scientists studying the effects of potentially
carcinogenic factors in the environment. Thus,
studies are related primarily to three major
program areas within the DCCP: biologic car-
cinogenesis, chemical/physical carcinogenesis,
and epidemiology.

The binational programs on which the DCCP
collaborates provide significant epidemiologic
opportunities for cancer research. This year,
joint studies and exchange programs enabled
scientists of the Cancer Institute Hospital in
Beijing to pursue clues drawn from the recent
county-based maps in China and to study the
changing risks among Chinese migrants to the
United States. Reports were prepared on the
geographic correlations within China between
cancers of the cervix and penis and colorectal
cancer and schistosomiasis and on the patterns
of childhood cancer in Chinese populations
around the world. Collaborative analytic inves-
tigations on cancers of the esophagus and lung,
trophoblastic neoplasms, and T cell leukemia are
also being developed.

Through a contract with the DCCP, scientists
at the Chaim-Sheba Medical Center in Israel are
determining the incidence of cancer in 10,000
Israeli children irradiated for ringworm of the
scalp, in 10,000 nonexposed persons selected
from the general population, and in 5,000 non-
exposed siblings. This effort is of significance in
the study of patients irradiated for benign dis-
eases because it allows an evaluation of biologic
mechanisms for carcinogenesis in humans. The
minimal confounding effects of carcinogenic
influences, and the possibly greater suscepti-
bility of young people to environmental carcin-
ogens, improve the chances of detecting radio-
genic effects and provide an opportunity for
lifetime studies of cancer incidence.

1^3

Table 'J-7.--NCI-PAHO collaborative cancer treatment research program
by location and number of active protocols

Active protocols

E
o

•4->

■<3

1 n)

■o

c
m

■V
n)

3
C

■D

£
o

E
o
u

i)
+-•

■!-•

1
"o

PAHO nation and center

>%
J

Argentina GATTS ^

GATLA ^

ROFFO

Brazil Rio de Janeiro

Sao Paulo

Chile

Colombia

Mexico

Peru

Uruguay

Total

2
5
2
1
1
2
1
1
8
3
26

^ Grupo Argentino de Tratamiento de los Tumores Solidos - Hospital Militar Central
° Grupo Argentino de Tratamiento de la Leucemia Aguda

Division of Extramural Activities

Grants by the DEA have been made available
to institutions and organizations in 1 1 foreign
countries. The scientific investigations under the
59 DEA grants include both basic and applied
research and range across the spectrum of the
thrusts and objectives of the NCI. Among these
are the National Research Council of Canada's
assays for and studies of the action of carcino-
gens and "promoters" of carcinogenesis. Other
studies being pursued in Canadian universities
and institutions include the pathogenesis of liver
cancer induced by chemicals, the role of anti-
tumor action of nitrosoureas, DNA repair/
replication in chemical carcinogenesis, the me-
tabolism and carcinogenicity of haloaromatic
pollutants, and melphalan interaction with amino
acids in human cells. At the University of Lon-

don a study is underway on the metabolic ac-
tivation of the polycyclic hydrocarbons as well
as a study of the therapeutic response of human
tumor xenografts. In Finland, at the University
of Helsinki, investigations are being pursued of
natural and tissue-specific immunity to human
neoplasms and fibronectin and its loss in malig-
nant transformation. Scientists at the Weizmann
Institute of Science in Israel are studying the
control of gene expression in tumor viruses and
in cells. At that institution, as well, studies are
underway of receptors and growth factors for
neoplastic cells and the modulation of cellular
responses by membrane fluidity.

These research grant activities provide the
NCI with opportunities to associate with and
take advantage of the foreign expertise available
in basic and clinical research that is directly
relevant to the thrusts and goals of the NCI.

Chapter V

National Heart, Lung, and Blood Institute

Introduction

The United States plays an important role in
international efforts to control heart, lung, and
blood diseases. This role has evolved through the
contributions of the U.S. scientific community,
in concert with the U.S. national programs ini-
tiated under the 1972 mandate from the Presi-
dent and the Congress. The mandate, while sig-
nificantly broadening the scope and depth of the
programs of the National Heart, Lung, and Blood
Institute (NHLBI), also created new opportunities
for U.S. scientists to collaborate with scientists
engaged in similar efforts in other countries. The
concerted government and private sector efforts
implemented in the United States in recent years
have resulted in significant improvements in the
health of the U.S. population. While mortality
rates for coronary heart disease are increasing in
many countries, they have been declining in the
United States. In recognition of this success, the
international medical research community hopes
to learn important lessons from the U.S. national
programs. Thus, scientists and administrators in
other countries frequently look to the United
States for expertise in research methodology,
design strategies, and implementation of re-
search findings at the community level. Con-
versely, through the Institute's international
programs, U.S. scientists are able to carry out
comparative studies and analyses not possible
through national efforts alone. A number of
bilateral agreements have been drawn up that
combine U.S. resources with those from other
countries on a cost-sharing basis.

The broad goals of the NHLBI international
programs are

• To develop international programs relevant
to the goals and priorities of the U.S. na-
tional programs in heart, lung, and blood
diseases and blood resources; and

• To develop international contacts, activi-
ties, and programs of mutual interest and
benefit to the United States and to the
cooperating country or countries in areas
related to the Institute's national mission.

The NHLBI international programs emphasize
basic research to enhance data generated in

domestic studies, clinical investigations, design
and implementation of epidemiological studies,
and programs in prevention, education, and con-
trol. By combining international resources with
national resources, scientists can use scarce
research funds more effectively in the United
States as well as in the collaborating countries.
Joint studies by U.S. and foreign scientists with
complementary skills, approaches, or resources
accelerate scientific research by consolidating
the management of the research problem, en-
suring comparability of data, and generally im-
proving the analysis of data.

NHLBI international programs have impacts on
health problems in the United States and abroad.
A growing network of countries is interested in
studies similar to those implemented by the
NHLBI. The Lipid Research Clinics studies are
an example of the strong international effort in
arteriosclerosis. Under NHLBI sponsorship, epi-
demiological data have been collected since
1972-73 on populations in the United States,
Canada, Israel, and the U.S.S.R. Analyses of the
data and publications of the results are contin-
uing. These studies compare lifestyles to genetic
determinants of cardiovascular disease, with
specific emphasis on the prevalence of lipid
disorders in different populations. Perhaps the
most important contribution of these studies is
the international standardization of data col-
lection and analyses. These procedures are also
being used to organize similar studies in China
and Poland so that future comparisons between
the United States and these two countries will be
possible as well. In a similar study sponsored by
PAHO, clinics in Mexico, Brazil, and Jamaica
will be standardized to generate comparable
data on nutrition and cardiovascular diseases in
Latin America and Caribbean populations.

Broad international interest in hypertension
has also been generated. The success of the
Institute's National High Blood Pressure Educa-
tion Program (NHBEP) and the Hypertension
Detection and Followup Program (HDFP) has
contributed to this interest. For instance, the
Federal Republic of Germany is using these
programs as models for its High Blood Pressure
Education Program initiated in 1980. Activities
planned under the U.S. -Kuwait Technical Coop-
eration Program in Health also build on the
experiences gained in the NHBEP and HDFP.

Studies of hypertension are important compo-
nents of the bilateral programs with China,
Japan, and the U.S.S.R. Each of these bilateral
programs provides unique opportunities for ex-
panding the knowledge base gained from U.S.
national data. In the case of the U.S. -U.S.S.R.
program in hypertension, the joint studies em-
phasize biobehavioral research. The U.S. -Japan
studies focus on the role of nutrition, while the
U.S.-P.R.C. cooperation explores the factors
that may be responsible for the observed dif-
ferences in rates of hypertension in north and
south China.

The above examples show how studies initiated
by NHLBI have generated interest in other
countries and international organizations in
testing similar hypotheses in a multinational
context. The insights resulting from these anal-
yses can lead to a broader understanding of the
relative importance of diet, heredity, lifestyle,
and environment in the etiology of cardiovas-
cular disease. These studies may also lead to new
approaches to the treatment and prevention of
cardiovascular disease.

Although NHLBI international activities in
basic research are conducted on a relatively
small scale, results can have important impli-
cations for the broader scientific community.
Research results from U.S. cooperation with
Italy, France, Japan, the Federal Republic of
Germany, and the U.S.S.R. are described in this
report.

One important impact of the NHLBI interna-
tional programs has been on the scientific lit-
erature. Under the bilateral programs, U.S.
scientists and foreign experts have collaborated
on many scientific publications, proceedings, and
books, making the information available to the
scientific community at large. These publica-
tions report on the results of joint planning of
research, joint implementation, and joint anal-
yses of data in a manner not possible through
national approaches alone. A number of proceed-
ings of U.S.-U.S.S.R. joint symposia were pub-
lished in FY 1982. Several books, reporting on
the results of U.S. -Italy joint cooperation, have
been published by Raven Press and Karger Ver-
lag. The proceedings of a U.S. -Poland joint sym-
posium on cardiovascular disease have also been
published. The first papers from the U.S.-P.R.C.
studies are being prepared for publication.

Summary of International Programs
and Activities

The Institute's international programs and
activities are carried out within the Institute's
mandates under the National Heart, Lung, and
Blood Program. The following sections summa-
rize NHLBI cooperative activities with other
countries during FY 1982.

Bilateral Agreements and Other
Country-to-Country Activities

Canada

Cardiovascular disease is the leading cause of
death in Canada, as in the United States. Mor-
tality from this disease has been declining in
both countries, although more rapidly in the
United States than in Canada. U.S. -Canadian
cooperation in areas related to NHLBI's mission
has been longstanding. Many NHLBI-sponsored
clinical trials have a Canadian component. In FY
1982, Canadian investigators participated in the
following studies:

• The Beta Blocker Heart Attack Trial: A
trial, completed in October 1981, that dem-
onstrated the effectiveness of the drug
propranolol in reducing mortality among
heart attack victims;

• Coronary Artery Surgery Study: A study to
evaluate the efficacy of coronary artery
bypass surgery in reducing morbidity and
mortality from heart disease;

• Lipid Research Clinics Program: An in-
ternational network of clinics conducting
the Coronary Prevention Trial to test the
hypothesis that reduction of serum choles-
terol in men with elevated cholesterol will
reduce coronary heart disease;

• Multiple Risk Factor Intervention Trial: A
prevention program to investigate whether
modification of three cardiovascular disease
risk factors—smoking, high blood pressure,
and elevated serum cholesterol—will reduce
the incidence of myocardial infarction and
death from coronary heart disease;

• Clinical Study of Intermittent Positive
Pressure Breathing: A trial to evaluate the
effects of this treatment when used as an
adjunct to the care of ambulatory patients
with chronic obstructive lung disease;

• Prevention of Neonatal Respiratory Dis-
tress Syndrome with Antenatal Steroid
Administration: A trial to determine
whether antenatal administration of steroids
can reduce the incidence, morbidity, and
mortality from this condition among infants
at risk.

China

An agreement between the Government of the
United States and the Government of the Peo-
ple's Republic of China on Cooperation in Sci-
ence and Technology was signed in January 1979.
The subsequent U.S.-P.R.C. Protocol for Coop-

eration in Science and Technology of Medicine
and Public Health, signed in June 1979, identi-
fied cardiovascular disease as one of the seven
areas of initial cooperation.

At the U.S.-P.R.C. Second Joint Science and
Technology Commission Meeting in October
1981, the U.S. cochairman noted that the coop-
erative program ranked with those of highest
priority to the United States and that the joint
activities were now yielding mutually beneficial
results. One such activity has been the develop-
ment of a joint protocol for collaborative re-
search on the epidemiology of cardiovascular
disease and its risk factors. The protocol defines
a study of urban and rural populations (men and
women) in north and south China. After comple-
tion of a pilot study in the spring of 1982, the
U.S. working group visited China in the fall of
that year to initiate the laboratory standardi-
zation program, train staff, prepare study forms,
and discuss data processing and methodology of
the biochemical measurements.

During FY 1982, a number of Chinese dele-
gations visited the NHLBI. In May 1982, a P.R.C.
study group on advances in research on athero-
sclerosis met with Institute staff to discuss
current research in atherogenesis, hypertension,
nutrition and cardiovascular disease, pathology,
and the Lipid Research Clinics Program. Later
that month the director of the new Beijing
Heart, Lung, and Blood Vessel Medical Center
and a member of his staff visited the NHLBI.
Two Chinese specialists in lung diseases held
in-depth discussions with the staff of the
NHLBI's pulmonary laboratories. In March, two
Chinese fellows completed a year of joint re-
search in the United States. The first of these
worked on the biochemistry of atherosclerosis
and prepared two papers for publication in
American journals. The topics are the quanti-
tation of apolipoprotein H in patients with dys-
lipoproteinemia and the quantitation and dis-
tribution of apo A-'f in familial dyslipopro-
teinemia. The second scientist performed cel-
lular studies of human atherosclerosis at the
University of Washington in Seattle.

Two Chinese fellows performed research in
the NHLBI's Pulmonary Branch with support
from WHO. The first of these scientists worked
on defining the role of the eosinophil in inflam-
matory lung disease and developed an animal
model useful for studying these diseases. She
presented her work at the American Thoracic
Society Meeting in May and an abstract was
published in the proceedings. The second sci-
entist worked on elucidating the pathogenesis of
fibrotic lung disease, one of the principal lung
diseases in China.

Egypt

Discussions of potential exchange activities
with Egypt continued during FY 1982. A number

of proposals from Egypt have been received in
recent years, primarily in hypertension and
rheumatic heart disease. Informal exchanges of
experts are underway in hypertension. Two visits
by Egyptian physicians took place in FY 1982.
Both experts were interested in the Institute's
programs in the cardiovascular area and in the
potential for future cooperation.

Finland

U.S. representatives reviewed a draft U.S.-
Finland Agreement for Health Cooperation de-
signed to strengthen existing links between the
scientific communities of the two countries and
to promote cooperation in health care and bio-
medical research. Future collaboration will
include exchanges of specialists and information,
organization of conferences and lectures, and
development of joint studies. During a visit to
the NHLBI by the Secretary General, Ministry of
Social Affairs and Health of Finland, in October
1981 the potential of future exchanges in the
cardiovascular area was discussed. Because
Finland and the United States are among the
countries with the highest rates of heart disease
in the world, both countries are emphasizing
prevention programs to deal with the problem,
and, in fact, informal exchanges of specialists
are underway.

France

The pathology of interstitial lung diseases has
been the focus of a number of joint studies under
the agreement between the NHLBI and INSERM.
This agreement was originally signed in 1970,
and in 1980 a 3-year project on interstitial lung
diseases was initiated between the NHLBI and
INSERM.

During FY 1982, two studies were completed
and the results submitted for publication: one on
histiocytic disorders and the other on hypersen-
sitivity pneumonitis. The first study was based
on the joint experiences of two French teams
and one American team. The second study of the
histological and ultrastructural features of hy-
persensitivity pneumonitis was based on the
findings of pooled lung biopsies obtained from 18
patients. A French scientist visited the United
States twice for joint experiments. She partic-
ipated in immunofluorescence studies of the skin
lesions in sarcoidosis, using monoclonal anti-
bodies. Upon her return to France, she applied
the techniques to cells collected by bronchoal-
veolar lavage as well as to samples obtained
surgically by open lung biopsies. Two reports are
being prepared for publication. Two U.S. sci-
entists made followup visits to Paris to continue
cooperative studies.

During FY 1982, the NIH-CNRS program sup-
ported a joint study to determine the role of the
natriuretic factor in the initiation and/or main-

tenance of essential hypertension in humans. The
natriuretic factor is a substance in the blood
that causes excretion of abnormal amounts of
sodium in the urine. Its structure, function, site
of formation, and factors causing its release into
the circulation are unknown. Direct and indirect
evidence suggests that sodium efflux from white
blood cells can be inhibited by the plasma of
hypertensive subjects but not by the plasma of
normotensive subjects. To confirm these obser-
vations, U.S. and French scientists are isolating
the natriuretic factor using new chemical iso-
lation techniques and bioassay procedures. Dur-
ing the course of this joint work plasma fractions
from hypertensive and normotensive patients
were analyzed. One fraction was found that
markedly inhibited the enzyme Na-K ATPase.
Further isolation and purification of the natri-
uretic factor is planned in order to produce
monoclonal antibodies that will then be used to
quantitate the factor in individual plasma sam-
ples. This work will continue in France. Once
sufficient quantities of the natriuretic factor are
prepared, the U.S. laboratory will examine pos-
sible physiologic roles for the substance and will
hope to offer new insights into its role in the
etiology of essential hypertension.

Federal Republic of Germany

Cooperative activities in cardiovascular re-
search are conducted under a joint U.S.-FRG
agreement between the Department of Health
and Human Services and the Federal Ministry for
Research and Technology of the Federal Repub-
lic of Germany, signed in 1976 and extended for
5 years in 1981. The emphasis is on linking on-
going projects in arteriosclerosis and hyper-
tension.

During joint scientific and health policy dis-
cussions held in the FRG in 1981, the following
cooperative activities were agreed upon for the
next 2 years:

• Internationally comparable surveillance and
monitoring of cardiovascular morbidity and
mortality and their association with risk
factors and health practices;

• Development and exchange of techniques
and strategies for intervention studies; and

• Development and exchange of techniques
for evaluation and validation of approaches
to intervention.

Since 1981, U.S. investigators have collabo-
rated with German scientists in the design and
planning of a Multicenter Intervention Trial
(MIT) and the German National Health Survey,
which will provide the necessary background
information for the MIT. The German MIT is an
8-year project. A 5-year trial will be preceded

by 2 years of pilot studies and followed by 1 year
of data analysis. To ensure that internationally
comparable data are obtained, U.S. and FRG
investigators have agreed to collaborate closely
throughout the studies.

Early in FY 1982, a German delegation visited
the NHLBI, the Central Patient Registry and
Coordinating Center for the Lipid Research
Clinics Program, and the National Center for
Health Statistics. A joint working meeting fo-
cusing on the German NHS and the MIT was held
at the NHLBI for a review of the protocols for
these activities. An in-depth joint analysis was
performed with special emphasis on standardi-
zing methods and procedures in the following
areas: laboratory procedures; electrocardi-
ography; health behavior assessment including
nutritional aspects and use of health services;
assessment of psychological factors; evaluation
of endpoints; and organization, management, and
data handling.

A second German delegation visited the
NHLBI to develop the syllabus for an advanced
2-week workshop in epidemiology funded by the
German Government. This workshop, to be held
in Germany in the fall of 1983, will be taught by
a combined U.S.-FRG faculty. The purpose of
this workshop is to develop the necessary epi-
demiological skills so that members of the MIT
staff can produce internationally comparable
surveillance and monitoring data. Also, late in
FY 1982, an FRG delegation visited several
community-based intervention projects in the
United States to develop and exchange strategies
for intervention studies and validate their pro-
posed approaches to intervention.

Because hypertension is a serious health prob-
lem in the FRG, as in the United States, the
German Government is taking steps to bring it
under control. Several exchanges have taken
place in this area. Because of the success of the
American HDFP, the Germans have initiated a
National High Blood Pressure Education Program
modeled on the U.S. program. In this way, they
hope to duplicate some of the declines in car-
diovascular disease experienced in the United
States in recent years. A German scientist
worked for a year with Hypertension Detection
and FoUowup Program staff in the United States
to develop the methodology for a pilot study for
the German equivalent. This cross-sectional
study, completed in FY 1982, was carried out on
men and women 30-69 years of age, drawn from
selected census tracts in Munich. Of the 3,198
persons selected for the pilot study, 2,216 in-
dividuals or 70 percent took part. One of every
three participants was found to be hypertensive
and nearly half the hypertensives {k5.Z percent)
did not know of their disease. Of those who
knew, only half were under treatment and of
these only one-third had their condition effec-
tively controlled. In summary, only 11.2 percent
of the hypertensive patients in the FRG pilot

study had their high biood pressure effectively
controlled at the onset of the program. The
study results illustrate the seriousness of the
problem and the feasibility of gathering inter-
nationally comparable epidemiological data. The
planned approach is envisioned as a multicenter,
cooperative, FRG-wide effort aimed at detect-
ing and treating all Germans who have hyper-
tension. Several basic research projects in the
area of hypertension are also being carried out
by individual U.S. and German investigators
cooperating informally.

The FRG Minister of Youth, Family, and
Health, who visited the NHLBI to discuss ongoing
cooperative studies with NHLBI staff, showed
particular interest in Institute programs to con-
trol hypertension.

Hungary

An Umbrella Agreement between the Hungar-
ian People's Republic and the Government of the
United States on Cooperation in Culture, Edu-
cation, Science, and Technology was signed in
October 1979. The agreement calls for exchange
and cooperation in areas of mutual benefit and
common interest.

Contacts between the United States and Hun-
gary continued during FY 1982. In July 1982, a
Summary of Discussion was signed for exchanges
of scientists in the cardiovascular area. Topics
include prevention and control of coronary heart
disease and hypertension, cardiac surgery, dia-
betes and heart disease, peripheral vascular
disease, noninvasive and invasive assessment of
left ventricular function, and pharmacodynamic
and pharmacokinetic studies with cardiovascular
drugs. Both sides agreed to exchange up to two
scientists each year for a total of 4 months.

India

The Director-General of the Indian Council of
Medical Research requested information from
the NHLBI on the Institute's strategic plan for
research in cardiovascular disease with a view
toward implementing a similar plan. The U.S.-
India Subcommission on Science and Technology
and Working Group on Medical and Health Sci-
ences met in December 1981 to discuss potential
areas of cooperation. A new initiative in scien-
tific and technological cooperation with India
was identified in 3uly 1982. The details of the
initiative will be worked out by a Blue Ribbon
Panel composed of eminent U.S. and Indian ex-
perts. The NHLBI has proposed that considera-
tion be given to rheumatic fever and rheumatic
heart disease in children, since the incidence of
these diseases is increasing rapidly in India. The
diseases, associated with high morbidity and
mortality, incur high medical costs.

Israel

The population of Israel offers unique oppor-
tunities for epidemiologic research. The diverse
ethnic and cultural backgrounds of the 3ews who
migrated there from many countries provide
important clues to the relative roles of genetics
and lifestyle in the etiology of cardiovascular
disease. The NHLBI has funded collaborative
research with Israel through grants and contracts
for over a decade. In January 1980, a 5-year
agreement for cooperation in health was signed
by the U.S. Department of Health and Human
Services and the Israeli Ministry of Health, and
efforts are underway to identify additional op-
portunities for cooperative activities.

In 1975, the NHLBI established the Jerusalem
Lipid Research Clinic to study the prevalence of
hyperlipoproteinemia among 17-year-old army
inductees and a subsample of their fathers. This
clinic, part of the international Lipid Research
Clinic Program, adheres to highly standardized
methods of data collection and analysis. The
Jerusalem population represents 55 countries of
origin and is divided into four broad groups:
Israeli, Asian, North African, and European/
American. Subject screening was completed in
1980.

Preliminary results show important differ-
ences in blood lipid profiles, which can be cor-
related with the country of paternal origin. Total
cholesterol levels were lowest in teenagers of
North African descent, highest in youths of
European and Israeli origin, and intermediate in
those from Asia. Triglyceride levels were lowest
among North Africans, but Asian and Israeli
groups had higher values than the Europeans.
Mean plasma high density lipoprotein cholesterol
levels were highest among youths with fathers of
European and American origin and lowest in
those of Asian and North African descent. Sec-
ond generation Israelis ranked intermediate
between the two groups. Thus, patterns of lipid
and lipoprotein levels previously observed in
adult immigrants persist into a generation of
native-born Israelis. These results were consist-
ent with the observed differences in the dietary
intake of total fat, saturated fat, and choles-
teroL The highest intake of these nutrients was
found in children of native Israeli or European/
American fathers. Comparison of the Israeli diet
with that of a group from the U.S. clinics showed
relative intakes of fat and saturated fatty acids
to be lower and carbohydrate higher than in the
United States. Ischemic heart disease incidence
and mortality in Israeli ethnic groups correlated
well with group mean total cholesterol values.

The results of the Jerusalem study will be
published as a monograph of the Israel Journal of
Medical Sciences . Preparation of data analyses
for this publication was the major effort during
FY 1982. The monograph will describe lipid and
lipoprotein profiles by country of origin, dietary

patterns, sociodemographic characteristics in
relation to various cardiovascular risk factors,
and distribution and characteristics of dyslipo-
proteinemias in the Jerusalem population.

Collaborative analyses comparing U.S. and
Israeli data were begun in September 1982 fol-
lowing the site visit of a U.S. team to Jerusalem.
Priority topics include comparisons of food and
nutrient consumption, diet and plasma lipid and
lipoprotein associations, incidence of coronary
heart disease, and resting and exercise ECG
studies.

The NHLBI also supports a joint American-
Israeli Migrant Study of like-sex siblings, one of
whom migrated to Israel while the other re-
mained in the United States. Approximately
2,^00 Israelis and 1,525 North Americans were
given a complete physical examination to deter-
mine whether differences in cardiovascular risk
factors are influenced by genetic and/or envi-
ronmental factors. Data analyses of this com-
pleted study are underway.

Italy

U.S. -Italy cooperation in cardiovascular re-
search was initiated in 1978 upon the signing of
the Joint U.S.-Italy Memorandum of Under-
standing by the Secretary, DHEW, and the Italian
Minister of Health in Rome in November 1977.
The Fifth U.S.-Italy Joint Symposium, entitled
"Methods of Noninvasive Diagnosis in Cardiovas-
cular Disease," was held in November 1981 in
Bethesda, Maryland. The purpose of this meeting
was to review currently available noninvasive
techniques and to assess their role and future
potential in the early diagnosis and monitoring of
cardiovascular disease. Discussions of imaging
techniques included comparisons of the levels of
sensitivity, accuracy, speed, and availability of
alternative methods as well as the quality of im-
ages and data produced by different procedures.

The noninvasive systems reviewed included
technologies capable of structural, functional,
biochemical, and mechanical assessment of the
cardiovascular system in health and disease.
These systems draw on images and computerized
data generated by X-ray, radioisotope, ultra-
sound, and nuclear magnetic response approaches
that provide information about structures and
events within the cardiovascular system. For
each technique, the theoretical basis underlying
the method, the advantages and disadvantages of
the procedure, and its current and potential
capabilities to assess changes in the arterial
walls were considered. Also, the panel reviewed
the potential of each technique to assess the
clinical significance of atherosclerotic lesions as
evidenced by end organ changes in blood flow,
metabolism, perfusion, structure, function, and
mechanical properties. These new methods are
expected to strengthen preventive and research
activities in cardiovascular disease and provide

the necessary information to prove conclusively
whether a given drug, dietary regimen, surgical
procedure, or other therapeutic approach has a
positive effect on the control of this disease.

During FY 1982, an Italian exchange fellow
worked for 3 months in the laboratory of a U.S.
scientist. The joint collaboration supports the
theory that the endothelium may contribute to
drug- and hormone-induced vasodilation, perhaps
through the release of an unidentified endogen-
ous vasodilator. The investigation is aimed at
determining the vascular site of action of hy-
dralazine, a widely used vasodilator and anti-
hypertensive agent. The results of this collabo-
rative study indicate that the endothelium may
play an important role in the vasodilator effect
of hydralazine.

The Italian coordinator for the U.S.-Italy
exchange program visited the NHLBI in 1982 to
discuss plans for the next joint symposium
scheduled for the fall of 1983 entitled "Endpoints
for Cardiovascular Drug Studies," with presen-
tations addressing chemical, epidemiological,
and direct observation endpoints. The proceed-
ings of the U.S.-Italy Joint Symposium on Nutri-
tion and Cardiovascular Disease are being pub-
lished by S. Karger AG, Basel.

A U.S. exchange fellow will work in Italy from
September to November 1982 to continue the
joint work on the blood vessel wall in hyperten-
sion with his Italian counterpart. The visit rep-
resents a unique opportunity to study this prob-
lem by means of a bioassay that the Italian sci-
entist has developed and refined, a "superfusion
bioassay system" capable of detecting extremely
low concentrations of substances with musculo-
tropic activity.

Japan

U.S. and Japanese scientists have enjoyed a
long history of successful informal cooperation
in the study of cardiovascular diseases. Hyper-
tension is a major problem in both countries, but
in Japan the most prevalent sequela is stroke,
while in the United States heart attack is the
most frequent outcome. Another point of con-
trast is in the lipid levels of the two populations,
which have been increasing steadily in Japan but
declining in the United States during the last
decade. The study of these differences is the
main focus of U.S.- Japanese collaboration.

A U.S. -Japan Umbrella Agreement in Science
and Technology in Non-Energy Areas was signed
in 1980 and includes cooperation in research on
cardiovascular disease. The agreement provides
a mechanism for formalizing and expanding the
joint research that has been in progress between
the two countries for over a decade. In February
1982, in the first official meeting under the 1980
agreement, Japanese and U.S. scientists met to
discuss and plan the joint activities. Five topics
were agreed upon for joint investigation: further

promotion of information exchanges on epide-
miological and experimental studies of hyper-
tension; experimental research on the prevention
of hypertensive diseases, especially nutritional
prevention and its mechanisms; epidemiological
analyses on hypertension and related cardio-
vascular diseases, including the evolution of
hypercholesterolemia and hypertension in the
young, and comparison of cerebrovascular and
cardiovascular diseases; epidemiological analyses
of risk factors, especially dietary risk factors
and studies of applicable standardized method-
ology for assessment of nutritional intake; and
further exchange of information on community
health control programs and intervention studies,
including dietary modification of blood pressure
control.

The next U.S.- Japan meeting will be held in
December 1982 in Japan, where the focus will be
on discussions of problems in standardizing epi-
demiological and nutritional studies of hyper-
tension, as well as experimental studies on the
prevention of hypertension through nutrition
control. A joint symposium now planned will give
U.S. scientists a broader view of Japanese
research in the field.

Japanese scientists have developed several
important animal models for studying hyper-
tension, atherosclerosis, and hyperlipidemia.
Recent interest has focused on the Watanabe
Hereditary Hyperlipidemic rabbit, a particularly
good model for studying familial hypercholes-
terolemia. In 1982, NHLBI scientists initiated
contacts with their Japanese counterparts to
explore the possibility of further joint study of
this model.

NHLBI and Japanese scientists have collabo-
rated since 1966 on studies involving the Stroke-
Prone Spontaneously Hypertensive Rat (SHR-SP),
a model originally developed in Japan. SHR-SP
animals that were fed the standard NIH rat diet
had a considerably lower incidence of stroke
than rats of the same strain that were fed the
standard Japanese diet. The main difference in
the diets was in their protein content, and the
"stroke protection" may be due to an increased
intake of certain sulphur-containing amino acids
and aromatic amino acids. Recent human epi-
demiological studies in Japan have also shown
the importance of dietary protein in the devel-
opment of stroke. Other investigators are study-
ing the role of sodium (Na) and potassium (K), as
well as the Na:K ratio, in the development of
hypertension. Japanese and American scientists
are cooperating on a continuing project entitled
"Experimental Studies and Dietary Prevention of
Hypertension and Atherosclerosis," funded by the
NHLBI and Japanese research institutes. The
Japanese coinvestigator visited the NHLBI in
1982 for joint experiments on the preventive
effect of methionine feeding on the subsequent
development of hypertensive disease. At the
Annual Meeting of the Hypertension Specialized

Centers of Research, he presented some new
results on the role of sodium and potassium in
hypertension. One of his findings is on salt-
accelerated platelet aggregation in general as
well as in healthy volunteers with a family his-
tory of hypertension.

The Honolulu Heart Program, begun in 1970, is
a 10-year study of prospective coronary heart
disease and stroke in 8,006 men of Japanese
ancestry living in Hawaii. On the basis of 10-
year heart disease incidence and mortality data,
this population was found to be intermediate
between the high levels of a similar cohort living
on the U.S. mainland and the lower levels of one
living in Japan. However, stroke incidence was
three times greater in the native Japanese co-
hort than in the Honolulu sample. The former
group also had a strong negative correlation
between cancer (particularly colon cancer) and
serum cholesterol levels. A 10-year reexamina-
tion of 2,000 men from the Honolulu sample was
completed in 1982. Data analyses now underway
should shed further light on the relative roles of
genetics and environment in the development of
cardiovascular disease.

Kuwait

An agreement for the U.S.-Kuwait Technical
Cooperation Program in Health was signed in
May 1981. In its preparation of a National Health
Plan, Kuwait is seeking consultant help to devel-
op a National High Blood Pressure Education
Program and to carry out epidemiological base-
line studies and followup monitoring of the pop-
ulation after disease intervention. Kuwait has a
relatively high prevalence of hypertension with a
low control rate and a rapidly increasing cardio-
vascular death rate. A U.S. consultant who vis-
ited Kuwait in February 1982 made recommen-
dations for an improved hypertension control
program. Next, a Kuwaiti delegation visited the
NHLBI in March 1982 to discuss the plans for the
project. The visit to Kuwait of an NHLBI rep-
resentative in April 1982 then resulted in a pro-
tocol for improved hypertension control. The
goals of this effort are to reduce deaths and
illness associated with uncontrolled hyperten-
sion, to reduce the proportion of persons at risk
due to elevated blood pressure, to increase the
number of health professionals who are trained
in the use of the recommended hypertension
management protocol, and to increase the
Kuwaiti capability to track and evaluate prog-
ress in hypertension control.

Nigeria

An Agreement for U.S. -Nigeria Cooperation in
Biomedical Research was signed in September
1981. Cooperative activities with the NHLBI
have been proposed in hypertension and in sickle
cell disease.

Poland

The NHLBI cooperates with Poland under two
separate agreements: the U.S.-Polish Agreement
for Health Cooperation, signed in 1973, and the
U.S. -Poland Collaborative Research Agreement,
signed in 1976 and supported by the Marie Sklo-
dowska-Curie Fund. Activities under the second
agreement were temporarily suspended during
FY 1982 because of the political situation.

Under the 1973 agreement, activities in three
cooperative areas devoted to basic, clinical, and
epidemiological research continued in FY 1982.

Area 1. Basic Research in Etiological Mech-
anisms; The Metabolic Fate and Function of
Prostacyclin.— Prostacyclin, a vasodilatory
prostaglandin produced in the arteries, is thought
to be important in preventing the formation of
blood clots. Prostaglandins also seem to affect
the circulation as mediators of hormone systems;
thus, their role in hypertension is under intense
investigation. From November 1981 to January
1982, a Polish scientist continued joint pharma-
cologic research in the United States on platelet
aggregation techniques and prostacyclin metab-
olites. It had previously been reported that an
enzyme present in platelets transforms the labile
antiaggregatory compound, prostacyclin (PGI2),
to a more stable compound, S-keto-PGEj. The
present study was directed toward characteri-
zing a previously unrecognized intermediate in
this pathway. It is hypothesized that the anti-
aggregatory activity of PGI2 may be due to this
unknown intermediate substance. This work is
important to our understanding of thrombosis
and to the development of drugs to prevent it.

Area 2. Clinical Research; The Diagnosis and
Treatment of Cardiomiopathy .— Plans were made
for the U.S. coordinator to spend 1 month in
Poland next year for continued joint inves-
tigations.

Area 3« EpidemioloRJcal Research; The Car -
diovascular and Clinical Correlates of High-
Density Lipoproteins .~A cooperative study has
been set up to explore the differences in cardi-
ovascular disease and risk factor trends between
Poland and the United States. Nearly 5,000 men
and women aged 35-6't will be screened in War-
saw and Cracow. The U.S. and Polish coordin-
ators met in October 1981 to discuss the pro-
posed study design and protocol; agreement was
reached on all the elements that will be studied.
A final study protocol is now being developed.
Two Polish scientists will visit the United States
in the fall of 1982 to learn laboratory standard-
ization procedures and to study methods of
lipoprotein measurement for use in the joint
study.

Under the U.S.-Poland Collaborative Research
Agreement, the NHLBI has supported two sepa-

rate studies. The first of these is the Polish Trial
in Multifactorial Prevention of Coronary Heart
Disease, part of a WHO-sponsored European
trial. During the U.S. coordinator's visit to Po-
land in May 1982, the results of the preventive
program to reduce coronary heart disease risk
factors in selected factory workers were ob-
tained and reviewed. The reduction of coronary
heart disease risk factors in high-risk men was
greater than in the general factory population.
Other data analyses are underway.

The second activity in progress under this
agreement is the Followup Study of Chronic
Nonspecific Respiratory Disease, to be made in
Cracow. This 13-year prospective study is ex-
pected to yield important data on this disease.

Spain

A 5-year Treaty of Friendship and Cooperation
between Spain and the United States was signed
in January 1976 and renewed in FY 1982. The
NHLBI has expressed interest in collaboration in
cardiovascular diseases and in blood banking and
blood resources.

Sweden

In FY 1982 exchanges between the United
States and Sweden focused on bringing U.S. and
Swedish investigators together for discussions of
data bases of potential interest to both nations.
Data on patients with Pi.ZZ emphysema, a very
rare disease, have been collected in both coun-
tries. By collecting as much information as pos-
sible on this combined group of patients, sci-
entists hope to learn more about the course of
this disease and the benefits of treatment.

United Kingdom

During FY 1982 data collection was completed
on the British Norwegian Migrant Study, in which
73,88^^ men and women in the United States,
Britain, and Norway were surveyed by mail to
determine the prevalence of angina and other
cardiorespiratory symptoms. A publication cur-
rently in press reports the analysis of factors
associated with angina-related mortality. Other
research being prepared for publication concerns
mortality differentials due to cigarette smoking
and mortality differentials due to cardiores-
piratory symptoms. Persons remaining in Britain
and Norway reported the symptom of angina
more frequently than did the migrants to the
United States. During a 5-year period following
the survey, angina was found to be a strong
predictor of cardiovascular mortality. In the
absence of angina, the migrants had a mortality
rate similar to nonmigrants, regardless of coun-
try of origin. However, the British had higher
mortality rates from cardiovascular and non-
cardiovascular causes than did the Norwegians.

The primary determinant of angina prevalence
was found to be migration status. It is believed
that those who migrated constitute a healthier
group than those who did not migrate.

U.S.S.R.

During FY 1982, U.S.-U.S.S.R. cooperation
continued under the bilateral health agreement
signed in 1972 and renewed in 1977 and 1982.
Cooperation is underway in eight areas of mutual
interest and need. During the 10 years of coop-
eration, 54^ specialists were exchanged. More
than 100 U.S. and Soviet institutions have par-
ticipated in the exchange, more than 60 in the
United States and ^0 in the U.S.S.R. Twenty-two
joint symposia have been held, and the proceed-
ings have been published (or are being prepared
for publication) in both English and Russian.
Nearly 700 scientific reports, abstracts, and
related articles have been published under the
auspices of the exchange.

Area 1. Pathogenesis of Atherosclerosis .—
This is a multidisciplinary, multiclinic research
program on the metabolism and epidemiology of
plasma lipids and lipoproteins as they relate to
atherosclerotic disease. The collaboration is an
extension of the NHLBI-sponsored Lipid Re-
search Clinics Program; it involves the partic-
ipation of nine U.S. lipid research clinics and two
clinics in the U.S.S.R. (Moscow and Leningrad).
In addition to geographic diversity, the popula-
tions selected for joint study in both countries
cover broad ethnic, occupational, and age ranges
making a variety of cross-cultural comparisons
possible. Important differences in cardiovascular
risk factors between the Soviet and American
study populations have emerged. The possible
causes of these differences are being explored to
clarify further the relationship between
cardiovascular risk factors and deaths in both
countries.

Extensive information has been collected and
analyzed on the prevalence of hyperlipopro-
teinemia in men ages W-59. The results were
presented at the First Joint Lipoprotein Sympo-
sium in May 1981 and will be published in both
countries late in 1982. A 5-year followup to
determine the cardiovascular status in a selected
subsample of these middle-aged men is now in
progress. A second prevalence study on a broader
population sample, men and women ages 20-69,
was initiated in 1978. Subject screening in this
phase was completed in May 1982. All the data
have been collected by rigorously trained per-
sonnel according to common protocols, using
highly standardized laboratory and screening
techniques.

In May 1982, the results of the first preva-
lence study on middle-aged U.S. and U.S.S.R.
men were presented at the Sixth International
Symposium on Atherosclerosis in Berlin. The

distributions of plasma total cholesterol, tri-
glycerides, and high density lipoprotein (HDL)
cholesterol differ significantly between the U.S.
and U.S.S.R. sample populations. Both the ^^0-^9
and 50-59 year age groups in the U.S.S.R. had
significantly higher mean values for plasma total
cholesterol and significantly lower mean plasma
triglyceride values. The higher mean levels of
plasma total cholesterol in the U.S.S.R. sample
may be attributable in part to the higher con-
sumption of dietary cholesterol and saturated fat
and to the lower consumption of polyunsaturated
fat in that country compared to the United
States. This difference in consumption patterns
may also account for the higher triglyceride
levels found in the U.S. sample. Both U.S.S.R.
age groups also had significantly higher HDL
cholesterol levels. This form of cholesterol has
been associated with a decreased risk of coron-
ary heart disease. The U.S.S.R. ^0-49 year age
group also had significantly higher mean low
density lipoprotein (LDL) cholesterol values.
LDL has a strong positive relationship to coron-
ary heart disease. The higher mean HDL choles-
terol levels in the U.S.S.R. may reflect an
aggregate of environmental factors.

The association of HDL cholesterol with other
cardiovascular risk factors was also studied. In
both countries, lower HDL cholesterol levels
were associated with obesity and carbohydrate
consumption, while moderate alcohol consump-
tion was associated with higher levels. Other
population studies have demonstrated that HDL
cholesterol levels are lower in cigarette smokers
than in nonsmokers. The findings here show that
the U.S. data support this link, while in the
Soviet men the association was either nonsig-
nificant or weak. Further investigation of these
differences is planned.

During the visit of a U.S. scientist to the
U.S.S.R. in November 1981, drafts of three joint
manuscripts were developed from data presented
at the First 3oint Lipoprotein Symposium. Data
analysis is also underway on blood pressure,
clinical chemistry tests, smoking, and exercise
electrocardiogram findings. A paper entitled
"U.S.S.R. and U.S. Nutrient Intake, Plasma
Lipids, Lipoproteins, and Nutrients in Men Ages
40-59 Sampled From Lipid Research Clinics
(LRC) Populations" will be presented at the
American Heart Association meetings in Novem-
ber 1982. The findings show that the Soviet men
had higher dietary intake of kilocalories, satur-
ated fats, cholesterol, and carbohydrates, while
the American men had greater values for pro-
tein, fat, and polyunsaturated fatty acids.

A U.S. working group visited Moscow and
Leningrad in December 1981 to review screening
procedures in the prevalence study; data col-
lection and mortality classification procedures in
the followup study were also discussed. A Soviet
biochemist visited the United States for 2
months to work on independent studies of HDL

subfractionation and on the composition and
function of HDL apoproteins.

The large investment of resources in this
collaborative area is now producing tangible
results. Eight years of data collection have cul-
minated this year in the completion of subject
screening and observation of important contrasts
between the U.S. and U.S.S.R. study populations.
Future plans include continued analysis of data
from the second prevalence study and continu-
ation of the 5-year followup study. A new em-
phasis on basic research is planned to investigate
questions raised by the epidemiological findings.
Directions for this research will be developed at
the next 3oint Steering Committee meeting.

differential intensive medical care in the
U.S.S.R. in the intensively treated patient groups
who also share similar initial characteristics.

The data on all patients in both the United
States and the U.S.S.R. are stored in the com-
puter facilities at the Data Coordinating Center
in Seattle. The study protocol specifies patient
followup through 3une 1983. Followup data on
the clinical status of the sample are forwarded
to the Coordinating Center twice a year. Com-
pletion of initial analyses of the data is antici-
pated by the fall of 1982 when a joint working
meeting will be held in Moscow. Those attending
this meeting will review and evaluate the data
from the joint study, interpret preliminary
results, and discuss opportunities for further
cooperation.

Area 2. Management of Ischemic Heart
Disease .— During FY 1982, cooperation con-
tinued on the collection and analysis of data on
American and Soviet patients participating in
joint studies of different approaches to the man-
agement of advanced coronary heart disease.
The therapies under investigation include "dif-
ferential" intensive medical management in the
U.S.S.R., "conventional" standardized medical
management in both countries, and coronary
bypass surgery in the United States. The study
includes a total of 1,648 patients carefully se-
lected according to joint criteria. Approximately
one-third of the patients are from the Soviet
Union, and two-thirds are from the United States.

One group of patients in both the United
States and the U.S.S.R. is precisely described by
symptoms, coronary angiograms, and a variety of
other characteristics. These patients, who con-
stitute the "reference" groups, are being treated
by conventional methods. Another group of pa-
tients with somewhat different coronary angio-
graphic characteristics is being treated in the
United States by coronary artery surgery and in
the U.S.S.R. by differential "intensive" medical
management. The "reference" group in each
country and the two "intensively treated" groups
are each composed of men from 30 to 60 years
of age. In the United States, the joint study
includes analysis of data from patients under-
going surgical treatment who have one or more
coronary arteries occluded by lesions causing an
obstruction greater than 70 percent. In the
Soviet Union, data are analyzed from patients
with comparable heart disease who are treated
by a specialized pharmacological regimen.

The joint study of these American and Soviet
patients will assess whether subjects in the ref-
erence group in both countries, who met the
same criteria and are treated in a generally
similar fashion, have similar characteristics on
admission and similar outcome on long-term
followup. If this similarity does exist, then there
will be a basis for comparing the long-term
effects of surgery in the United States with

Area 3. Myocardial Metabolism .— Basic
research to develop information that may lead to
improved methods for prevention and treatment
of cardiac diseases is the objective of Area 3.
3oint studies are underway on the mechanisms of
energy transfer within cardiac cells and on the
ways that these cells respond to oxygen defi-
ciency. Other studies concern the factors that
regulate cardiac growth, the coordination of
contraction within cardiac cells, the response of
cardiac cells to changes in their microenviron-
ment, the visualization of cardiac muscle dam-
age due to oxygen deficiency, and the effective
rapid transport of drugs to damaged heart
muscle.

Teams of American and Soviet collaborators
have carried out joint research projects spanning
a number of years. The research is carried out
jointly in U.S. and U.S.S.R. laboratories, enabling
both sides to contribute techniques unique to
their respective countries. As a result, new
information has become available more rapidly
than would have been possible without such
cooperation. The English language proceedings of
the Fifth U.S.-U.S.S.R. Symposium, which were
published in FY 1982, contain reports on the
cooperative projects. Also during this year,
several joint articles have appeared in major
U.S. and Soviet journals. Titles include "Ca2+-
Dependent Interaction of 5-Dimethylamino-
naphthalene-1-Sulfonyl Calmodulin with Cyclic
Nucleotide Phosphodiesterase Calcineurin and
Troponin I," "A Study of Actin Fibronectin In-
teraction," "Chromatographic Studies on Inter-
conversions of 'Non-Activated' and 'Activated'
Forms of Glucocorticoid Receptor Complexes
from Rat Heart Cytosal," and "A Structural
Study of Filamin, a High-Molecular-Weight
Actin-Binding Protein From Chicken Gizzard."

Three U.S. scientists conducted joint research
in the U.S.S.R. in FY 1982. One worked on
lipoprotein genes and on the effect of gluco-
corticoids on myocardial calcium metabolism.
3oint research protocols were drafted, and a

5tt

jointly authored article was prepared. The sec-
ond U.S. scientist continued joint research and
completed a joint publication, entitled "Creatine
Kinase of Heart Mitochondria: Changes in Its
Kinetic Properties Induced by Coupling to Oxi-
dative Phosphorylation." Both scientists made
presentations at the Ninth World Congress of
Cardiology in Moscow. A third U.S. scientist
continued joint work on structural proteins of
cells, including studies on spectrin. He prepared
and took to the Soviet Union a large quantity of
pure spectrin, a cytoskeletal protein of red blood
cells. The collaborating Soviet scientist con-
ducted physical chemistry studies on this protein.

Two Soviet scientists visited the United States
during FY 1982. One continued joint studies on
targeted drug transport to damaged cardiac cells
employing drug-loaded liposomes. In 1978, the
Soviet investigator together with a U.S. col-
league succeeded in linking antibodies specific
for cardiac myosin to liposomes. When cardiac
muscle is damaged by lack of oxygen, intra-
cellular antigens are uncovered that are recog-
nized by this liposome-antibody complex. By
adding an isotopic marker to the drug liposome
complex, scientists can visualize the damaged
muscle at the same time as the therapeutic
agent is rapidly and preferentially applied to it.
Results of these joint studies have been pub-
lished in major U.S. and Soviet journals. A sec-
ond application of the Soviet-developed lipo-
somes is being studied both in the United States
and the U.S.S.R. A U.S. biochemist has syn-
thesized a potent renin inhibitor to be used as a
potential antihypertensive agent. However, this
peptide is metabolized within minutes after
injection into laboratory animals. It is hoped that
this breakdown of the active compound can be
delayed by encapsulating it into liposomes. The
U.S.-developed peptide has been sent to the
U.S.S.R., where it will be linked to liposomes.
These collaborative studies are aimed at the
development of a long-acting injectable renin
inhibitor suitable for use in the treatment of
hypertension. The other Soviet scientist studied
advanced nuclear magnetic resonance techniques
to measure metabolism in the intact heart and to
begin a joint research project in this area.

Three senior U.S. investigators visited the
U.S.S.R. in 1982 to present papers and exchange
research findings in areas of mutual interest.
The topics included regulation of protein turn-
over in skeletal and heart muscle, regulation of
amino-acid catabolism, regulation of microtu-
bule assembly and distribution in eukaryotic
cells, calcium regulation of cytoskeletal func-
tions, mechanisms of mitosis and chromosome
movement in eukaryotic cells, molecular dif-
ferentiation of the myocardium, and the mech-
anism of heart morphogenesis. Also, the U.S.
coordinator for Area 3 visited the U.S.S.R. to
plan the next joint symposium to be held there in
1983.

Area 4. Congenital Heart Disease .— Coop-
erative activities in this area center on the
surgical treatment of complex heart defects as
well as on methods of diagnosis and postopera-
tive care to reduce mortality from congenital
heart disease.

A three-member Soviet delegation including
the U.S.S.R. Coordinator for Area ^ visited the
United States and met with U.S. counterparts to
discuss plans for further cooperation and to
review the results of the latest research on this
cardiovascular disease problem. Plans were made
for the Fifth Joint U.S. -U.S.S.R. Symposium on
Congenital Heart Disease to be held in May 1983
in the United States.

Surgical techniques were discussed during the
delegation's visit to U.S. clinics and cardiovas-
cular centers. Both sides reviewed their exper-
iences with heart transplants and surgical pro-
cedures to control arrhythmia. The Soviets have
an active surgical program for arrhythmia, and
interest was expressed in joint discussions of
indications for surgery and also of valve re-
placement as possible topics for future joint
collaborative activities.

In 3uly 1982, a U.S. scientist visited the
U.S.S.R. to meet with the U.S.S.R. Coordinator
for joint discussions on cardiorespiratory physi-
ology and postoperative care. He lectured at
Soviet medical institutions on the topics of acute
respiratory failure, postoperative respiratory
failure, and general principles of intensive care
of the critically ill patient.

Area 5. Sudden Death .— A disturbance in heart
rhythm is believed to be the immediate
mechanism of sudden death, which constitutes a
leading cause of mortality in the United States
as well as in the U.S.S.R. U.S.-U.S.S.R. collab-
oration is designed to learn more about the
mechanisms of arrhythmias and about the inter-
vention of antiarrhythmic agents to regulate the
heart's electrophysiologic functions.

During FY 1982, joint activities included the
Third Joint U.S.-U.S.S.R. Symposium on Sudden
Death held in Kaunas, Lithuania, June 1982. In
December 1981, the U.S.S.R. coordinator and his
colleague from Kaunas visited the United States
to complete plans for the symposium. An eight-
member U.S. delegation participated in the
symposium and also attended the Ninth World
Congress of Cardiology in Moscow. Symposium
topics included recognition of risk associated
with arrhythmias, reversible coronary artery
obstruction, pathobiology of acute myocardial
ischemia, sensory functions of the heart, modu-
lation of adrenergic activity of the heart, vari-
ations in morphology of the atrioventricular node
and His bundle of the human heart, neurological
and humoral aspects of sudden death, and the
possible protective effect of neuropeptides in
animals susceptible to sudden death when placed
in conflict situations. A joint paper was pre-

sented on an ongoing exchange of epidemiolog-
ical data to determine if certain populations in
each country may provide a "laboratory" for
investigating national mortality trends in each
country. The U.S. investigators had learned that
in local areas time trends of the incidence of
acute myocardial infarction, one of the most
important clinical components of ischemic heart
disease (IHD), parallel national mortality trends.
The joint presentation reported the results of
investigations of data from medical histories and
from clinical, electrocardiogram, and laboratory
studies of patients with acute myocardial in-
farction in Oakland, California, and compared
these data with those of patients included in the
registry of acute myocardial infarction in
Kaunas, Lithuania. A number of differences were
noted in electrocardiographic and serum enzyme
studies. Nevertheless, percentages of cases
classified as definite and possible acute myocar-
dial infarction among the U.S. and Kaunas
patients were similar. Through the study and
comparison of long-term trends in the two na-
tions, we expect a better understanding of the
factors affecting development of ischemic heart
disease and sudden death.

Further exchanges of scientists are planned in
six areas: pathological anatomy, electrophysi-
ology of sudden death, study of the effects of
antiarrhythmic drugs, clinical aspects of sudden
death, epidemiology of sudden death, and higher
nervous and peripheral nervous activity in ven-
tricular arrhythmias and sudden death.

Area 6. Blood Transfusion .~The exchange in
Area 6 focuses on research on blood and blood
products for transfusion and treatment of dis-
ease. In the past, the emphasis in Area 6 has
been on hepatitis, posttransfusion hematological
complications, and blood substitutes. However,
in recent years the range of collaboration has
broadened, encompassing thrombosis and hemo-
stasis in general, with particular emphasis on
platelet abnormalities as well as on hemophilia
and other genetic bleeding disorders.

In December 1981, a three-member Soviet
delegation visited the United States to exchange
information and data on procedures for blood
donor processing, blood components, and prep-
aration of platelet concentrations. U.S. and
Soviet scientists discussed a possible joint proj-
ect for isolating and studying vesicles shed by
red cells during storage and for quantitative
analysis of their membrane proteins. It was
agreed that prior to shipping specimens from the
U.S.S.R. to the United States, preliminary
studies on the stability of vesicle preparations
would be completed in Moscow. In the area of
hepatitis, the Soviets are studying the specific
immunology of anti-A as well as anti-B
hepatitis. The visit of the Soviet delegation
provided opportunities to discuss future collab-
oration on the use of Factor VIII in the treat-

ment of hemophilia, red blood cell preservation,
and long-term preservation of platelets.

A U.S. scientist visited the Soviet Union in
April 1982 to lecture on genetics and hemoglob-
inopathies and to discuss modern laboratory
techniques of gene manipulation. The visit pro-
vided an opportunity for the Soviet Central
Institute of Hematology and Blood Transfusion
and the NHLBI to exchange information on cur-
rent developments in molecular biology research
on thalassemia and to plan future collaborative
activities.

During the fall of 1982, a U.S. scientist visited
the U.S.S.R. to continue joint studies in the area
of hematapheresis. This collaboration compared
platelet collection procedures and patient trans-
fusion response to platelets collected by con-
tinuous flow cell separation techniques; com-
pared recipient response to leukocyte-rich single
donor platelets ("Aminco") and leukocyte-
depleted platelet ("IBM-2997") concentrates and
patient response; measured efficiency of cyto-
reduction procedures using "Aminco" and "IBM-
2997" blood cell separators in patients with blood
diseases (thrombocytosis and leukocytosis); and
determined the frequency of leukapheresis and
platelet pheresis to reduce risks of cerebrovas-
cular accidents.

The new U.S.S.R. chairman for Area 6 and his
U.S. counterpart met in August 1982 during
meetings of the International Hematology and
Blood Transfusion Societies to discuss plans for
exchanges and studies. These plans will be de-
veloped further during the Ninth Working Meet-
ing in Area 6 scheduled for December 1982 in
the United States. At that time, the U.S. and
U.S.S.R. representatives will also plan the pro-
posed program of the Third Joint Symposium on
Blood Transfusion to be held in the U.S.S.R. in
1983.

Area 7. Hypertension .— Begun in 1977, joint
activities in this area have focused on the ex-
change of information, exchanges of scientists,
joint working meetings, and joint symposia on
the clinical, psychophysiological, behavioral,
epidemiological, and preventive aspects of
hypertension.

The Proceedings of the 1981 Joint U.S.-
U.S.S.R. Symposium on Hypertension; Biobe -
havioral and Epidemiological Aspects are cur-
rently being prepared by the U.S. side for pub-
lication in English and by the Soviet side for
publication in Russian. They will include 10
Soviet papers and 7 U.S. papers.

In July 1982, two U.S. scientists visited the
U.S.S.R. to develop plans for a joint study on
psychological interventions and the role of the
sympathetic nervous system in primary hyper-
tension. This collaborative study assesses neur-
oendocrine and blood pressure changes resulting
from biobehavioral treatment strategies. Spe-
cifically, the study will determine if nonpharm-

acological interventions (hypnosis, biofeedback,
transcendental meditation, and relaxation tech-
niques developed by the Soviet side) can reduce
blood pressure in patients with primary hyper-
tension classified according to psychological
profiles developed in the United States.

In accordance with the Summary of Discus-
sions signed at the 1981 symposium, a joint
working meeting on biobehavioral treatment of
hypertension is scheduled for the fall of 1982 in
the U.S.S.R. Three topics of collaboration are
being developed in this area— basic, clinical, and
community intervention studies. In each of these
areas, resource groups of experts have been
identified to facilitate future scientific ex-
changes and to develop a productive exchange
program between U.S. and Soviet laboratories.

Area 8. Artificial Heart Research and Devel -
opment. — U.S.-U.S.S.R. collaboration in the
development of artificial heart and circulatory
assist systems recognizes that present and
foreseeable treatments still leave a substantial
number of patients with compromised or fatally
impaired heart function. The development of
supportive mechanical devices to assume some
and eventually all of the pumping function of the
failing heart is the long-term goal of this coop-
eration.

During April 1982, the U.S.S.R. Chairman for
Artificial Heart Research and Development
visited the United States to discuss mechanically
assisted circulation. Six areas of proposed coop-
eration were identified: the study of the mech-
anisms of interaction of biomaterials with blood
and its components and the development of
comparability criteria for evaluating biomater-
ials' hemocompatibility; comparative evaluation
of the condition of the myocardium by means of
biochemical and morphological tests during
one- or two-sided bypass; comparative evalua-
tion and development of new methods of con-
necting various pump devices for two-sided
bypass; exchanges of specialists and delegations
in order to continue further joint activities in
assisted circulation, artificial heart control
systems, and biomaterials; publication of joint
articles on U.S.-U.S.S.R. activities and scientific
data exchanges; and plans for the Third and
Fourth U.S.-U.S.S.R. Symposia on Artificial
Heart and Assisted Circulation in the U.S.S.R. in
1983 and in the United States in 1985.

Two publications were generated from U.S.-
U.S.S.R. cooperation in this area during FY 1982.
A joint paper entitled " In Vitro Evaluation of
U.S. and U.S.S.R. Artificial Hearts" was pub-
lished in Artificial Organs , the journal of the
International Society of Artificial Organs, in
May 1982. A Soviet article describing an im-
plantable artificial heart driven by a compact
motor was received by the U.S. side and trans-
lated for review by U.S. investigators.

In accordance with a previous agreement, the

U.S. side provided the U.S.S.R. counterparts with
biomaterials in exchange for the control system
received from the U.S.S.R. in 1981. Plans for the
future call for continued exchanges of scientists
from each side to conduct joint in-depth evalu-
ation of the blood compatibility of several fre-
quently used biomedical polymers by means of in
vitro techniques.

One of the outcomes of U.S.-U.S.S.R. coop-
eration in the cardiovascular area is the publi-
cation of the Journal of Soviet Cardiovascular
Research , published by Plenum Press. This Eng-
lish language journal, now in its third year of
publication, contains articles translated from
Kardiologia and other Soviet journals on the best
Soviet research in the cardiovascular area.
Articles are selected by an editorial board com-
posed of U.S. and Soviet scientists, including
several of the coordinators for the eight areas of
U.S.-U.S.S.R. cooperation in the cardiovascular
field.

Venezuela

A Joint U.S. -Venezuela Science and Technol-
ogy Agreement was signed in October 1979.
Venezuelan scientists have a strong interest in
cooperation in the cardiovascular area, partic-
ularly in clinical research. Possible collaborative
efforts are being considered in Chagas' disease,
which is endemic in rural areas of Venezuela and
in other South American countries. Chagas'
disease infects children at an early age, and a
large proportion of these patients develop car-
diomyopathy several years later.

Venezuelan and NHLBI investigators are de-
veloping a protocol to study Chagas' disease.
During FY 1982, the director of the Venezuelan
institute established to prevent, detect, and
treat this disease worked with NHLBI epidemi-
ologists on protocol development, data handling
methodology, and the design of instruments to be
used in this study. Later in FY 1982, the Direc-
tor, Centro Pan Americano de la Investigacion y
Adiestramiento de Enfermedades Tropicales
(CEPIALET), who is also the Venezuelan coor-
dinator for the U.S.A.-Venezuela Cooperative
Agreement, visited the NHLBI to discuss the
Chagas' project with Institute staff.

Venezuela is one of the countries interested in
developing uniform international standards for
the biomaterials used for human prostheses. To
facilitate both national and international stand-
ardization, the NHLBI has produced biomaterial
standards for distribution to interested inves-
tigators. Samples of these U.S. biomaterial
standards have been requested by Venezuelan
investigators.

Yugoslavia

Coronary heart disease (CHD) can result from
the interaction of a number of environmental,

behavioral, genetic, and physiological factors.
Because Yugoslavia is undergoing rapid indus-
trialization, scientists are concerned about in-
creased coronary heart disease.

Several studies on this problem have begun as
a result of the agreement signed between the
United States and Yugoslavia in 1973. During FY
1982, plans were completed for a study entitled
"An Epidemiological Study of Secular Trends in
CHD Risk Factors." This study uses data from a
population in Tuzla, a suburb of Zagreb, pre-
viously studied for many years under the project
"Incidence of Hypertension and Coronary Heart
Disease." The objectives of the new study are to
determine whether cigarette smoking, hyper-
tension, and electrocardiographic abnormalities
are increasing in Yugoslavia. The study will
include a repeat examination of part of the
original cohort in Tuzla, as well as an examina-
tion of two younger cohorts (aged 35-^^^), one in
Tuzla and one in Belgrade. Two U.S. scientists
visited Yugoslavia in April and May 1982 to
discuss technical aspects of the study to ensure
comparability of the Yugoslav data with U.S.
data. The computer capabilities of the Institute
of Chronic Diseases and Gerontology in Belgrade
were reviewed as well as procedures for data
analysis.

By measuring risk factors over an extended
period of time in cohorts of similar age, this
study will examine whether the industrialization
and urbanization process is accompanied by
changes in physiological characteristics. It will
also provide information on changes in the prev-
alence of CHD. If an increase in CHD is ob-
served, the study will ascertain how much might
be due to changes in the known risk factors. The
study will also seek to determine which changes
in the study population's environment are the
most important for developing CHD.

Cooperation With International Agencies

During FY 1982, the NHLBI continued its
active cooperation with international agencies.
Since 1980, the Institute has been a WHO Re-
gional Collaborative Center for Research and
Training in Cardiovascular Diseases for the
Americas. In this capacity, the NHLBI provides
advisory services for WHO, and collects and
exchanges information on cardiovascular dis-
eases. The Institute also assists in the place-
ment of WHO-sponsored fellows from different
countries.

The NHLBI is collaborating with WHO on the
Multinational Monitoring of Trends and Deter-
minants in Cardiovascular Diseases (MONICA), a
new health information system to measure heart
disease incidence by collecting longitudinal,
cross-cultural data on cardiovascular disease risk
factors. NHLBI epidemiologists assisted in
designing the study protocol. Pilot studies were
completed in 1981 in four communities where

the formal study is now underway. Other
MONICA'S will be launched in 1983 in eight
additional countries.

Plans for other cooperative activities between
the NHLBI and WHO were considered. In 3uly
1982, the WHO representative for genetic dis-
eases met with NHLBI staff to discuss possible
future collaboration on sickle cell disease. WHO
is interested in implementing programs in Africa
to address this problem. The Chief of Cardio-
vascular Diseases at WHO visited the NHLBI in
April 1982 to discuss areas of continuing coop-
eration. The Assistant Director for International
Programs, NHLBI, met with WHO officials in
Geneva to discuss its programs on cardiovascular
disease prevention and control.

The NHLBI and WHO have also exchanged
information concerning WHO's Integrated Pro-
gram for the Prevention and Control of Noncom-
municable Diseases. The objective of this pro-
gram is to improve the health of total communi-
ties with respect to noncommunicable diseases
through an integrated approach to health pro-
motion. The NHLBI has provided WHO with
information on its intervention and health edu-
cation programs relevant to the WHO effort.

At the request of PAHO, Institute staff par-
ticipated in a workshop entitled "Contribution of
Dietary and Pharmacological Interventions in the
Prevention and Control of Cardiovascular Dis-
eases" in March 1982. This workshop brought
together investigators from Brazil, Chile, Ecua-
dor, Jamaica, Mexico, and Trinidad to plan the
project. Responding to a number of questions
regarding the proposed design of the study, In-
stitute staff gave advice based on Institute ex-
perience with similar projects. Among the
questions discussed was the strength of the evi-
dence that an increased intake of polyunsatur-
ated fatty acids coupled with a decreased intake
of saturated fatty acids to bring the dietary
ratio close to 1 (P/S ratio = 1) results in both
lowering blood pressure (systolic and diastolic) in
normal as well as in mildly hypertensive popu-
lations and reducing the tendency to thrombosis.

Two PAHO fellows from Thailand visited the
NHLBI in May 1982, one of whom is the Chair-
man for Planning and Organization for Preven-
tion and Control of Cardiovascular Disease in
Thailand. They toured U.S. medical and research
facilities to study the planning, organization, and
research aspects of the prevention and control of
cardiovascular disease. Also, in FY 1982 two
U.S. scientists—one individually and the other as
part of a WHO team—visited Thailand to con-
tinue joint scientific discussions.

Extramural Programs

During FY 1982, the NHLBI awarded 6 con-
tracts and 17 grants to the following countries:
Argentina, Australia, Canada, Denmark, Israel,

Romania, and Sweden. These awards supported
mainly cooperative epidemiological studies on
foreign components of national clinical trials.
Ten fellowships were awarded to U.S. scientists
for training in the following countries: Belgium,
Canada, Israel, Sweden, Switzerland, and the
United Kingdom. These young American re-
searchers took their training outside the United
States to capitalize on unique research oppor-
tunities available in chosen foreign institutions.

Human red blood cell production is basically
under the control of the erythropoietin hormone.
Extensive studies of this hormone are underway
in the United States. These studies require hu-
man erythropoietin, which is best obtained from
the urine of anemic patients. In certain areas of
Argentina, iron-deficient anemia due to hook-
worm is endemic. The NHLBl is supporting the
collection, purification, and study of this hor-
mone from these patients. The Institute also
makes available erythropoietin for study by U.S.
researchers.

The Institute is supporting research on the
genetic epidemiology of precursors of human
hypertension in a migrant Polynesian population.
This longitudinal study is designed to identify
factors that cause an increase in blood pressure,
lipid levels, obesity, and other risk factors of
cardiovascular disease. The Tokelu Island Mi-
grant Study is an epidemiologically based in-
vestigation of the changes in physical and socio-
cultural environment that are associated with
increased risk of cardiovascular disease, as
Tokelauans migrate from their traditional atolls
to New Zealand. The study is unique in that the
population was surveyed before migration was
completed in 1968 and both the nonmigrant
population (in Tokelu) and the migrant population
(in New Zealand) are subject to longitudinal
followup. Migrants showed a considerable in-
crease in the prevalence of hypertension and a
less marked increase in mean blood pressure.
Obesity, which is increased in the migrants, is
clearly a factor in their elevated blood pressure.

International Conferences, Seminars,
and Meetings

A conference titled "Nutrition and Blood
Pressure Control: Current Status of Dietary
Factors and Hypertension" was held in Septem-
ber 1982. NHLBI staff chaired several sessions,
and NHLBI grants and contracts supported the
research of many of the speakers. The symposi-
um provided a forum for communication among
health professionals, biomedical investigators,
and representatives of government and industry.
Scientists from Canada, the Federal Republic of
Germany, 3apan, the Netherlands, and the
United Kingdom took part in the discussions. The
role of sodium, potassium, divalent ions (calci-

um, magnesium, selenium, and other trace ele-
ments) on blood pressure was discussed. Other
topics covered were the effects of macronutri-
ents, alcohol, lipids, and carbohydrates on blood
pressure and diet as opposed to drug therapy for
hypertension.

An international workshop, "Changing Patterns
in Cardiovascular Disease in the Pacific Basin,"
was sponsored in January 1982 by the NHLBI in
Kona, Hawaii. Areas represented were Australia,
China, Fiji, Hawaii, Japan, Micronesia, Nauru,
Niue, New Zealand, the Philippines, Rarotonga,
Western Samoa, the United Kingdom, the United
States, and Taiwan. Approximately 35 scientists
and observers attended this workshop. Topics
included stroke risk factors such as salt, blood
pressure, and smoking; and demographic and
socioeconomic factors of CHD, rheumatic fever
and rheumatic heart disease, sudden death, and
diabetes. The Pacific Basin region offers a
unique opportunity to study how environmental
and genetic factors interact to influence the risk
of coronary heart disease, stroke, and hyperten-
sion. Of particular interest is the comparison of
cardiovascular risk due to patterns of migration.

"Implications of Recent Beta-Blocker Trials
for Post Myocardial Infarction (MI) Patients," a
workshop held at the NHLBI in May 1982,
reviewed and documented the state of knowledge
regarding the effects of beta-blocking agents in
post-MI patients to generate recommendations
for future research on beta-blocking agents and
to address questions regarding the implications
of recent beta-blocker trials. Results from on-
going long-term beta-blocker trials in Australia,
the Federal Republic of Germany, the Nether-
lands, Sweden, the United Kingdom, and the
United States were compared. Experts from
Ireland, Norway, Sweden, the United Kingdom,
and the United States presented findings on the
beneficial effects of administering these drugs
following an acute heart attack. The U.S. par-
ticipants presented the results of a randomized
trial of propranolol in patients with acute MI.
Thirty-six months following their acute MI,
patients receiving propranolol had a survival rate
significantly greater than that of a matched
group of patients receiving a placebo. The Swe-
dish workers reported similar favorable results
with metoprolol, another beta-blocker.

Intramural Programs and Activities

Joint research was carried out in laboratories
of the Division of Intramural Research, NHLBI,
by 63 foreign investigators who came from Aus-
tralia, Canada, China, the Federal Republic of
Germany, France, Greece, Hong Kong, India,
Ireland, Italy, Jamaica, Japan, Korea, Poland,
Sweden, Turkey, the United Kingdom, and
Taiwan.

The NHLBI intramural scientists and their
French counterparts have been undertaking joint
studies on the pathology of interstitial lung
diseases (see France). These studies have proven
valuable to both sides because they allowed
pooling of scarce lung biopsy material from
patients in both countries.

Active research cooperation of NHLBI intra-
mural scientists with their Japanese colleagues
has taken place since 1966 (see Japan). This
cooperative research is investigating the inter-
relationship of nutrition, hypertension, and

stroke; the researchers are using animal models
of hypertension, stroke, and hyperlipidemia
developed in Japan. These rat models of human
disease have provided much new information on
the basic etiology of these important diseases.

A scientist from the Biochemical Pharmacol-
ogy Section, NHLBI, conducted joint work in
Australia to determine the role of the brain
serotonergic system in the regulation of arterial
blood pressure, and on techniques, including
immunohistochemistry, applicable to the study
of blood pressure.

Chapter VI

National Institute of Arthritis,
Diabetes, and Digestive and Kidney Diseases

Introduction

The National Institute of Arthritis, Diabetes,
and Digestive and Kidney Diseases (NIADDK)
conducts and supports biomedical research in a
wide range of mostly chronic, often disabling,
disorders. In many instances, these activities
benefit from the contributions of members of
the international scientific community. Contin-
ued collaboration with international scientists, in
addition to funding of research with the poten-
tial for worldwide impact, remains an estab-
lished priority for the Institute.

Ongoing international programs of the Insti-
tute are targeted at such areas as nutrition,
arthritis, and thyroid hormone synthesis.
Regarding international cooperation on nutrition,
the Institute expects to increase an understand-
ing of the influence of the environment on nu-
tritional requirements; on the interaction of
nutrition, immune competence, and infection;
and on the health consequences of dietary pat-
terns. In the area of arthritis collaboration, one
goal is to ascertain the best drugs to treat
juvenile rheumatoid arthritis. Cooperation in
research into thyroid hormone synthesis might
result in an improved treatment of hypo-
thyroidism.

Through international cooperation and col-
laboration in areas such as these, scientists may
perhaps control, prevent, and ultimately elimi-
nate the many chronic and disabling disorders
fcJling within the purview of the Institute.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

Through the Bilateral Cooperative Agreements
Program, the NIADDK has developed collabo-
rative and cooperative activities with France,
Japan, and the U.S.S.R. These activities consist
of the U.S.-3apan Malnutrition Panel Research
Support Program, the U.S.-U.S.S.R. Cooperative
Program in Arthritis, and the NIH-INSERM
Agreement.

The following discussion outlines the status,
current activities, and accomplishments of the
collaborative programs with the three nations.

Japan

The Malnutrition Panel, a binational steering
committee of experts, was established in 1966 as
part of the U.S. -Japan Cooperative Medical
Sciences Program. The entire cooperative pro-
gram, which covers a number of different dis-
ease areas, is administered by the NIAID, but the
malnutrition portion is the responsibility of the
NIADDK Division of Digestive Diseases and
Nutrition, with significant support from the
NICHD.

Malnutrition continues to be a serious problem
in most Asian countries, the most common forms
of which are protein-calorie malnutrition and
deficiencies of iron and vitamin A. Also of con-
cern are various disease states, particularly
diarrheal infections, that impair the body's
utilization of some nutrients or lead to the ex-
cessive loss of others. These infections are the
major cause of death in children under 5 years of
age. Undernutrition also has a severely adverse
effect on the outcome of pregnancy, increasing
the number of infants born prematurely or with
low birth weight and with more disabilities and
inadequate nutritional reserves. Iron deficiency,
a widespread disorder in Asia, causes anemia and
all its attendant symptoms. It may also interfere
with normal immune responses and may lower
resistance to infection. Vitamin A deficiency is
responsible each year for many thousands of
cases of impaired vision and total blindness in
children.

The five priority areas of focus of the Malnu-
trition Panel are:

• Influence of environmental and host factors
on nutritional requirements;

• Health significance and methods of pre-
venting iron deficiency;

• Interaction of nutrition, immune compe-
tence, and infection;

• Effects of nutrition on physical and mental
development, behavior, physical capability,
and work performance; and

• Health consequences of different (and
changing) dietary patterns and food habits.

An announcement was made in FY 1982
regarding the availability of grant support for
studies on "Environmental and Host Factors
Affecting Nutritional Requirements." In August
1981, a workshop was held in San Diego, Cali-
fornia, entitled "Opportunities for Collaborative
Research Relating to Nutritional Requirements
in Asian Countries." In attendance were nutrition
scientists from Bangladesh, Burma, China, India,
Japan, Malaysia, New Guinea, Thailand, the
United Kingdom, and the United States. The U.S.
Malnutrition Panel has also collaborated with the
Japanese Malnutrition Panel to organize a work-
shop, "Practical Approaches to Eradication of
Subclinical Iron Deficiences," which was held in
Tokyo on December 7 and 8, 1982.

Recent findings from a number of nutrition
research grants supported by the NIADDK and
other NIH Institutes and identified as relevant to
the U.S.-3apan program are listed below:

Zinc — An important ongoing study at the
University of Colorado has shown that low
dietary zinc intake is a specific environmental
factor that may contribute to poor linear growth
velocity in children. This effect was observed in
a double-blind controlled study of liO preschool
children. Dietary zinc supplementation signif-
icantly increased linear growth velocity in the
boys, but not in the girls.

Another study, at the University of Texas,
suggests that a zinc-dependent enzyme, RNase,
may be an appropriate means of monitoring zinc
status in man. A group of young adult men were
fed a zinc-deficient diet for 8 weeks, during
which the activity of RNase was found to in-
crease significantly in the parotid saliva and
blood plasma during zinc depletion and return
toward normal with zinc repletion.

Iron .— In a study funded at the University of
California at San Francisco, decreased red blood
cell (RBC) survival in iron deficiency has been
observed in association with increased RBC
membrane stiffness. Decreased RBC deforma-
bility in iron deficiency was shown to be due
primarily to decreased membrane viscoelas-
ticity. Iron-deficient RBC's showed increased
susceptibility to peroxidation and showed evi-
dence of spontaneous membrane lipid and protein
cross-linking. These conditions suggest that
increased RBC membrane stiffness in iron de-
ficiency may be related to peroxide damage and
is responsible for the observed decrease in RBC
survival.

In other studies on the effect of iron status on
immunity in neonatal and maternal rats, results
reveal that individual components of the immune
response are affected differently by iron defi-
ciency. While circulating immunoglobins (IgG or
IqM) are resistant to change, the development of
lymphoid organs such as the thymus and spleen is
profoundly affected by iron deficiency, which
may alter permanently the immunocompetence
of the organism.

Vitamin A .— At Tufts University, a rapid dark
adaptation test has been developed that can be
used under field conditions on children as young
as age four. This method, which is very sensitive
to vitamin A deficiency, involves matching the
intensities of colored discs to the function of the
cones in the eye (not rod function), so that under
dim lighting conditions the ability to separate
the different colored discs is dependent on rod
function alone. This rapid dark adaptation test is
expected to become widely used in surveys to
identify subclinical vitamin A deficiencies.

In other studies relating to vitamin A, two
patients with markedly abnormal dark adapta-
tion, despite normal serum vitamin A and zinc
levels, experienced restoration of dark adapta-
tion to normal through protein repletion alone
(without supplemental vitamin A or zinc). These
results argue that protein status does affect the
ability of the retina to use vitamin A.

Protein-Energy Requirements .— Studies are
underway at Johns Hopkins University to assess
the growth, body composition, and protein status
of 6- to 36-month old infants on low, medium, or
high levels of protein intake in relation to die-
tary calories (from 4.7 to 8 percent calories
from protein). So far, results have not identified
significant differences in growth or body compo-
sition because the numbers are too small for
conclusive analysis. However, overall caloric
intake appears to rise progressively as the per-
cent of protein calories decreases. Also, changes
in proportion between calculated arm muscle and
fat cross-sectional areas favor the highest pro-
tein intake group.

At the Massachusetts Institute of Technology,
noninvasive stable isotopes (^-^C, ^h, l^N) have
been used to investigate the dynamic aspects of
whole body amino acid metabolism in adult
humans brought about by changes in intake of
dietary protein and energy. Results, indicating
that the synthesis of alanine is extensive and
increases under conditions of low protein and
high energy intake, suggest that alanine plays an
important role in the retention and recycling of
body nitrogen when there is a need to conserve
nitrogen. In contrast, changes in glycine metab-
olism do not appear to affect significantly the
maintenance of the whole body nitrogen econo-
my. In addition, this new technique is expected
to be of value in determining the requirements

for essential dietary amino acids in human sub-
jects.

U.S.S.R.

The U.S.-U.S.S.R. program of cooperation in
arthritis originated with the Health Exchange
Program of 1972, an agreement to improve col-
laboration between the two countries in public
health and medical service. In September 1973,
arthritis became a subject of cooperation under
this program. The program has three major
divisions: clinical studies in rheumatic disease;
studies in the basic science of rheumatic disease;
and orthopedic surgery for arthritis, with em-
phasis on clinical studies, using common, agreed-
upon protocols for the treatment of rheumatoid
arthritis and systemic lupus erythematosus.

Over 100 subjects in both the United States
and the U.S.S.R. are participating in an ongoing
trial, begun in August 1981, of the comparative
benefits of hydroxychloroquine and D-penicil-
lamine in treating juvenile rheumatoid arthritis.

Another study, at the University of California
at Los Angeles, addresses the "Assessment of
Methods for Measuring Hand Function in Rheu-
matoid Arthritis."

NIH-INSERM Agreement

Under an agreement between the NIH and
INSERM, substantial scientific collaboration has
occurred between the Clinical Endocrinology
Branch of NIADDK and the Unite de Recherche
sur la Glande Thyroide et la Regulation Hormon-
ale of INSERM. The exchange of scientists be-
tween the two centers has provided excellent
opportunities for collaborative research and the
effective use of trained personnel in the study of
thyroid hormone synthesis and metabolism. In-
vestigators from both the United States and
France have been working on separate but re-
lated aspects of thyroid physiology and biochem-
istry. Combining some of the resources available
to each group has greatly enhanced the progress
of research in these areas, and has led to the
evolution of new procedures for solving problems
of thyroid functions.

In FY 1982, two French scientists engaged in
collaborative research in a Clinical Endocrin-
ology Branch laboratory.

Extramural Programs

To use the expertise available through bio-
medical researchers in other countries and to
further the progress of knowledge in high-
priority health problems of international scope,
the NIADDK continues to support projects ini-
tiated by scientists located outside the United
States who apply directly to the Institute's
extramural research programs. In FY 1982, more

than 30 such projects in the form of research
grants, postdoctoral training grants, and coop-
erative agreements were active at the NIADDK.

International research funded by the NIADDK
has made many contributions to knowledge, in
both the clinical and basic science areas. For
example, in the area of end-stage renal disease,
work carried on at the University of Helsinki in
Finland is attempting to describe the structure
of inflammation in experimental and human
kidney allograft rejection and to use these
findings to develop new diagnostic methods for
monitoring and counteracting rejection episodes
in clinical transplantation. At the Karolinska
Institutet in Sweden, the NIADDK is supporting
prospective investigations into the metabolic
effects of continuous ambulatory peritoneal
dialysis.

Some other current projects abroad relate to
diabetes research. Research at Royal Southern
Memorial Hospital in Australia is attempting to
elucidate the genetic and environmental inter-
actions that make for susceptibility to non-
insulin-dependent diabetes mellitus (NIDDM).
The objectives of the project are: (1) to deter-
mine whether specific genetic markers exist in
the NIDDM diabetic or in individuals with pre-
disposing genes for diabetes; (2) to determine
whether the differing susceptibility of various
ethnic groups to NIDDM is related to the pres-
ence or absence of these genetic markers; (3) to
establish the relative roles of other factors such
as age, nutrient intake, physical activity, obe-
sity, and stress in the causation of NIDDM in
genetically susceptible individuals; and (^) to
identify possible preventive factors relating to
NIDDM in high prevalence populations. The
studies will be carried out in Caucasian, Mela-
nesian, Polynesian, Micronesian, and American
Indian populations. It is hoped that feasible in-
tervention programs might be defined on the
basis of future findings.

A project at the Chaim Sheba Medical School
in Tel Hashomer, Israel, is aimed at clarifying
the risk factors for human glucose intolerance.
The overall objectives are to quantify inter-
relationships, distinguish between causes and
effects, evaluate the relative role of environ-
mental and genetic factors, and understand the
temporal sequence of events among glucose
intolerance, obesity, and macro- and microvas-
cular complications of diabetes.

International Conferences, Seminars, and Meetings

Scientific meetings with an international
audience play a major role in the interchange of
biomedical information. They provide a forum
for the exchange of research findings and in-
formation among investigators from different
countries, and they often stimulate further sci-

entific collaboration. The NIADDK continues to
contribute toward the support of selected con-
ferences within the United States and abroad,
providing a setting for scientific cross-fertil-
ization among international investigators.

The International Society for Experimental
Hematology (ISEH) held its eleventh annual
meeting in Baltimore, Maryland, during August
1982. The ISEH is a relatively young organiza-
tion, which has grown to more than 500 members
in the past 10 years. Meetings are held each
year, alternating between the United States and
foreign countries, usually in Europe. Topics
presented at the Baltimore meeting included
bone marrow transplantation, hematopoietic
stem cell regulation, erthropoiesis, granulopoi-
esis, lymphopoiesis, effect of radiation on stem
cells, animal models for human hematopoietic
disorders, and effects of aging on the hemato-
poietic system. At past meetings of the ISEH,
presentations have been made by scientists from
such countries as Australia, Finland, the Federal
Republic of Germany, Israel, the Netherlands,
the United Kingdom, and Yugoslavia. As a focus
for the initial presentation of work from labor-
atories around the world, the annual meetings of
the ISEH are an important mechanism of inter-
national scientific exchange.

The NIADDK provided major support for the
Third International Congress on Nutrition and
Metabolism in Renal Diseases, which was held in
Marseilles, France, in September 1982. Previous
congresses have been established to disseminate
information about nutritional therapy to improve
the metabolic and nutritional disorders associ-
ated with chronic renal failure, both in patients
who are not treated with dialysis and in those
who are undergoing maintenance dialysis ther-
apy. Knowledge in this area having expanded
rapidly, the congresses have been designed so
that clinicians and researchers pursuing basic
and clinical investigations in various countries
could meet and discuss areas of mutual interest
and concern. The Organizing Committee of the
Third Congress was composed of individuals from
the United States, France, the Federal Republic
of Germany, and Italy. Topics addressed included
muscle and cellular metabolism in renal failure,
catabolic stress in renal failure, endocrinemet-
abolic disorders in acute and chronic renal
failure, nutritional and metabolic aspects of
continuous ambulatory peritoneal dialysis, con-
servative management of chronic renal failure,
techniques for prevention of progression of
chronic renal failure, nutritional management of
pediatric patients with renal failure, and the role
of sodium and potassium intake in the etiology
and management of hypertension.

The Institute supported a colloquium entitled
"Advances in Diabetes Epidemiology," which was
held near Paris, France, in May 1982. Additional
funding was provided by INSERM. The collo-
quium was particularly timely because of recent

efforts to establish uniform diagnostic criteria
for diabetes. These criteria have been adopted
by several organizations concerned with the
disease. A second development that made the
colloquium so relevant was the advent of popu-
lation-based registries. The meeting was an
attempt to pool data from all over the world in
light of considerable new information on the role
of viruses, autoimmunity factors, and histo-
compatibility antigens in the etiology and path-
ogenesis of diabetes. Also discussed were het-
erogenicity in each of the types of diabetes,
genetics, environmental etiologies of insulin-
dependent diabetes, and studies of blood glucose
levels in different groups and populations.

The colloquium was held under the auspices of
staff members of the Unite de Recherches Sta-
tistiques and other French institutions. In addi-
tion, there was a scientific committee composed
of members from Australia, the Federal Repub-
lic of Germany, and the United Kingdom,

The NIADDK provided grants for a number of
American scientists to attend the Twelfth In-
ternational Congress in Perth, Australia, which
was held in August 1982. Among the many topics
covered were enzymology, enzyme mechanisms,
protein synthesis, and the relationship between
structure and function of biologically relevant
molecules. Of high scientific quality, these tri-
ennial congresses of biochemistry play an im-
portant role in the progress of biochemical
research throughout the world.

Intramural Programs and Activities

Intramural scientists at the NIADDK engage in
a broad range of collaborative activities, both in
foreign laboratories and with scientists from
other countries who make use of the resources at
the NIH.

One program in which a number of intramural
scientists participate is actually an initiative of
governmental education authorities in Italy. It
involves both travel to the NIH by young Italian
scientists and corresponding visits to sponsoring
Italian laboratories by NIADDK staff.

At NIADDK, one laboratory carrying on col-
laborative work under this program has been the
Biochemistry of Cell Regulation Section in the
Laboratory of Biochemical Pharmacology.
Studies have been pursued on the structural
properties of the receptor for thyroid stimula-
ting hormone on normal thyroid plasma mem-
branes, on plasma membranes of human and
experimental thyroid tumors, and in strains of
differentiated thyroid cells grown in vitro . These
studies have established the role of glycoproteins
and glycolipids in receptor recognition, the
mechanism of message transmission, and the
relevance of their functional expression in nor-
mal and disease states such as goiter. Graves'
disease, and hyperthyroidism.

Research on vesicles coated with clathrin, a
protein that provides a mechanism to bring thy-
roglobulin and other substances into the cell, is
being done by an NIADDK clinical endocrinol-
ogist at the University of Naples.

A Fogarty Scholar-in-Residence from Japan is
one of the two or three preeminent scientists
involved in the chemical synthesis of peptides
and proteins. Thus far, he has spent about 6
months in residence at the NIH, acting as a
consultant to the Laboratory of Chemical Biol-
ogy (LCB). He has been involved in work with
NIH intramural scientists on the chemical syn-
thesis of interferon and on the synthesis of pep-
tides as inhibitors of the gelatin of sickle hemo-
globin. During this time, the group synthesized
and studied a number of peptides and tested
their efficacy as gelatin inhibitors.

Additional collaborative study of synthetic
peptide inhibitors of sickle hemoglobin gelatin is
ongoing between LCB scientists and a Nobel
Laureate at the Medical Research Council Lab-
oratory of Molecular Biology in Cambridge,
England. Using synthetic peptides synthesized at
the NIADDK lab, scientists are studying the
binding of several synthetic peptides to crystals
of hemoglobin to try to establish the mechanism
of their gelation inhibition. Once this informa-
tion is available, LCB scientists will design new
and probably longer peptides, with the assistance
of the molecular graphics system of the NIH
Division of Computer Research and Technology.

In a collaborative project with the Department
of Morphology at the University of Geneva,
Switzerland, the morphologic aspects of poly-
peptide hormone interaction with target cells of
insulin action, particularly in the liver, are being
studied. These are the first studies to combine a
biochemical approach and a physiologic approach
with morphologic probes to demonstrate surface
interactions and intracellular processing of
polypeptides.

Recent collaboration between the Nuclear
Magnetic Resonance Section of the Laboratory
of Chemical Physics and the Indian Institute of
Science in Bangalore has centered on the basic

molecular structure of peptides, using various
methods of spectroscopy and X-ray diffraction.

Another collaborative project involves the
Laboratory of Biochemistry and Metabolism and
the Weizmann Institute of Science in Rehovot,
Israel. An effort is being made to map the
three-dimensional structure of integral mem-
brane proteins, using spectroscopic techniques.
Integral membrane proteins, found in the phos-
pholipid bilayer of cells, actually perform most
of the active functions of the cell membrane.
Researchers have collaborated to study, among
others, bacterial rhodopsin, which is a unique
pigment that permits bacteria to use light to
generate energy (through the "proton pump"
mechanism). The investigators believe that find-
ing a way to inhibit the proton pump process may
enable us to inhibit viral interaction with cells
because the proton pump is always involved in
such interactions.

The NIH Visiting Program and Health Scientist
Exchange Program

Under the NIH Visiting Program, scientists at
the NIADDK sponsor investigators from many
countries to pursue work in laboratories on the
NIH campus, and in turn many NIADDK re-
searchers visit and collaborate in laboratories
and clinics abroad. As the inevitable result of
such a program, the cross-fertilization of ideas
has mutual benefits for the United States and
the foreign countries involved. Often it can lead
to new advances in biomedical research. The
following countries were represented in the
Visiting Program during 1982: Australia, Austria,
Bangladesh, Belgium, Canada, China, the Federal
Republic of Germany, France, Ghana, Greece,
Hungary, India, Israel, Italy, Japan, Korea, Mex-
ico, the Netherlands, New Zealand, Nigeria,
Pakistan, Poland, Portugal, the Republic of
South Africa, Spain, Sweden, Switzerland,
Trinidad, the United Kingdom, Yugoslavia, and
Zimbabwe.

Chapter VH
National Library of Medicine

Introduction

The international programs of the National
Library of Medicine (NLM) are a natural exten-
sion of NLM's domestic responsibilities. Coop-
erative in nature, these activities have relevance
to both the developed and the developing world.

The advancement of biomedical and health
research, education, and health care depends
upon effective biomedical and health communi-
cations. Through its activities, products, and
services, the NLM fills the important role of
coordinating biomedical and health information
as it collects, organizes, and disseminates this
information not only domestically but also glo-
bally. The U.S. health professional benefits from
the international character of the NLM collec-
tion, its data bases, and its functions; the world
health community derives benefit not only from
NLM's products but also from NLM's inter-
national collaborative undertakings.

NLM's international activities fall into six
general categories: literature exchange, library
services. Special Foreign Currency (P.L. ^80)
Program, MEDLARS cooperation, technical
consultation, and participation in international
organizations. Involving primarily a sharing of
time, talent, and resources, these activities
require a variety of mechanisms for execution,
but all have a common objective: to benefit the
U. S. health effort.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

International MEDLARS Agreement

NLM's international MEDLARS quid pro quo
arrangements have been in existence since the
first arrangements with the United Kingdom and
Sweden in 1 968.

There is no transfer of monies between the
participating country and the NLM. The NLM
makes available the MEDLARS system, technical
documentation, and training either through tapes
or online access to the NLM computer. The

participating country must meet technical cri-
teria involving personnel, equipment, and fiscal
resources and have a user community large
enough to justify an extensive computerized
service. The participating country then provides
and/or funds the indexing of journal articles for
input to the MEDLARS data base in return for
access to the system. This practice is consistent
with a policy adopted in 1966 by the Federal
Council for Science and Technology, which was
that Federal information systems would be made
available in return for some contribution.

The NLM does not select the institutions that
will serve as MEDLARS Centers. The country
itself makes that choice after meeting certain
technical criteria established by the NLM. The
MEDLARS Center may be in an organization
primarily concerned with medicine or health, in
a library, or within an organization broadly con-
cerned with science and technology. In all cases,
the foreign MEDLARS Centers function as a
national biomedical information resource.

A country has a choice of alternative
MEDLARS arrangements: it may operate the
system on its own computer using the NLM tapes
(with or without NLM software) or it may use
telecommunications linkages to access the NLM
computer. Table 7-1 lists the regions, organi-
zations, and modes of access.

The Karolinska Institutet of Sweden hosted a
meeting of policy officials from each of the
countries with MEDLARS Centers. The meeting
included a description from each of the officials
about recent developments, plans for the future,
quid pro quo arrangements, the role of govern-
ment in providing biomedical information, the
impact of technology, and the relationship
between developed and developing countries.

In their discussions of the role of the govern-
ment, the members of the International
MEDLARS Policy Advisory Group, which repre-
sents health-related scientific and educational
institutions and libraries in 12 countries, pre-
pared a statement recognizing the NLM's lead-
ership role and affirming that biomedical and
health information is basic to maintaining and
advancing biomedical and health research, edu-
cation, and care.

The Advisory Group's statement emphasizes
the value of the MEDLARS system, referring to
it as a national and international resource that

Table 7-1.— National Library of Medicine non-U.S. MEDLARS Centers

Region

Organization

Mode of
Access to
MEDLARS

Australia
Canada
Colombia
France

Germany (Federal
Republic)

Italy

Japan

Mexico

South Africa

Sweden

Switzerland

United Kingdom

Intergovernmental
Health
Organization

The National Library of Australia (NLA) Tapes/

Software

Canada Institute for Scientific and Technical Information Online NLM

National Research Council of Canada

FUNDACION OFA and FONDO COLOMBIANO de Online NLM

INVESTIGACIONES CIENTIFICAS (COLCIENCIAS)

Institut National de la Sante et de la Online NLM

Recherche Medicale (INSERM)
Ministere de la Sante Publique et de la Securite Sociale

Deutches Institut fur Medizinische Dokumentation Tapes

und Information (DIMDI)
Der Bundesminister fur Jugend, Familie und Gesundheit

Istituto superiore di Sanita Online NLM

Ministero della Sanita

3apan Information Center of Science and Technology (3ICST) Tapes
Science and Technology Agency

Centro Nacional de Informacion y Documentacion en Salud Online NLM

Ministerio de Salud

Institute for Medical Literature Online NLM

South African Medical Research Council

Karolinska Institutet Tapes/

Software

Schweizerische Akademie der Medizinischen Wissenschaften Tapes

The British Library Online NLM

Biblioteca Regional de Medicina (BIREME) Tapes/

Pan American Health Organization Software

assists and enhances medical research, educa-
tion, and health care delivery throughout the
world. The statement describes the MEDLARS
group of information services as an integral part
of the research cycle and an important support
to U.S. international relationships based on shar-
ing knowledge, expertise, and facilities through
bilateral arrangements. MEDLARS makes it
possible to disseminate medical information
efficiently and effectively to all countries, in-
cluding those of the developing world.

Special Foreign Currency Program

The Library's Special Foreign Currency Pro-
gram, authorized by P.L. 83-^80, as amended,
relies upon appropriations of U.S.-owned, local
foreign currencies to make awards for scientific
writing and publication projects in cooperating
countries, including Egypt, India, Israel, Paki-
stan, Poland, and Yugoslavia. The programs in
Israel and Poland were continued under collab-
orative bilateral research agreements.

Projects in the six cooperating countries in-
clude preparation of critical reviews and mono-
graphs analyzing biomedical research and prac-
tice; translations of foreign monographs in the
health sciences; studies in the history of medi-
cine; publication of major international symposia
and conference proceedings; and preparation and
publication of bibliographies, guides, and other
literature tools in the biomedical sciences. The
program enables the NLM to draw on foreign
scientific personnel and resources in obtaining
and disseminating information important to U.S.
health educators, practitioners, and researchers.

The projects are multiyear, and during FY
1982 89 studies were active. Over 50 percent of
the current program is carried out in Poland and
Egypt, with about 20 percent in India. New crit-
ical reviews and monographs in health fields
constitute ^-5 percent of the projects, with
projects concerned with the history of medicine
representing another 30 percent.

Among the new P.L. 480 projects activated in
FY 1982 were a critical review on the endocrine
system in patients with acute renal failure,
publication in Egypt of the seventh volume of a
major international bibliography of ticks and
tickborne diseases, and translation of a Russian
study of the geographical pathology of athero-
sclerosis. Among the publications received in FY
1982 resulting from prior support was a mono-
graph entitled Chronic Hemodialysis as a Way of
Life, written by two internationally renowned
experts and addressed to medical and psychiatric
practitioners. The book covers every aspect of
hemodialysis. Another study recently published
with support from the P.L. ^80 Program was an
English language translation of the last work of
the late Alexander R. Luria, a widely recognized
Soviet neuropsychologist; the book, translated in
India and printed in the United States, is called
Language and Cognition. Among the recently
published studies in the history of medicine was
Two Great Scientists of the Nineteenth Century;
Correspondence of Emil Du Bois-Reymond and
Carl Ludwig. This book presents a 30-year cor-
respondence between two of the most important
figures in the development of modern physiology
and offers an insight into 19th-century medicine.
The text was translated in Tunisia and printed in
India.

Activities With Interaational Agencies

World Health Organization

The NLM and the WHO Special Program for
Research and Training in Tropical Diseases con-
tinued to cooperate in the publication of the
Quarterly Bibliography of Major Tropical Dis -
eases. The NLM prepares camera-ready copy
that WHO prints and distributes to approxi-
mately 5,500 institutions in the developing
countries. The bibliography is prepared from the

MEDLINE system and covers those diseases WHO
had identified for special attention— filariasis,
leishmaniasis, leprosy, malaria, schistosomiasis,
and trypanosomiasis.

Furthermore, the WHO Program for Control of
Diarrheal Diseases requested NLM's assistance
in a Bibliography of Acute Diarrheal Diseases
which is planned for periodic publication. This
bibliography has been issued for the first time
within this fiscal year following the same pro-
cedure of NLM's production of camera-ready
copy from MEDLINE and WHO's printing and
distribution.

The NLM and WHO continued the collabora-
tive arrangement for provision of photocopy of
journal articles to developing countries of the
WHO regions of Africa, Eastern Mediterranean,
and Southeast Asia. Under this arrangement,
WHO supports one individual in residence at the
NLM to provide this service. This modest level
of activity responds only partially to the existing
biomedical and health information needs of
developing countries.

WHO has been actively working with devel-
oping countries to identify existing resources for
biomedical and health information and to de-
velop mechanisms for providing information
services. The Director of the National Library of
Medicine is a member of the WHO Advisory
Committee on Medical Research Subcommittee
on Biomedical Information. Included in the sum-
mary and recommendations of the final 1982
report of the subcommittee was the following
observation:

Regional and national medical libraries and
information networks to share scarce re-
sources are now being planned or are under
implementation or development in all regions
in close contact with Headquarters. Those
efforts are to be expanded and sustained as
they are a prerequisite for the successful
implementation of WHO health plans. The
model of resource sharing and network im-
plementation that is being developed by
BIREME should be examined for its potential
application in other areas of the world.

The Subcommittee is pleased that several
regions have or are preparing regional Index
Medicus, that PAHO and Headquarters have
developed document information services
using the "Medical Subject Headings" (MeSH)
vocabulary, and that SEARO and Headquarters
are planning a pilot project for the biblio-
graphic control of fugitive health literature on
health services research.

The Subcommittee recognizes that there
exist national literature, documents, audio-
visual materials, etc., which are not now ac-
cessible in an organized manner.... Efforts to
collect, organize and index such [fugitive]
material into bibliographic systems should use
the same internationally accepted cataloguing

rules and standards and MeSH, . . . resulting in
bibliographic systems and products in the
whole health field [which] will be compatible
with each other and with the regional and
global Index Medicus/MEDLARS.

The Subcommittee considers the selective
dissemination of bibliographic information
with abstracts as exemplified by the Quarterly
Bibliography of Major Tropical Diseases as an
important and cost-effective method to keep
health researchers in developing countries
informed about progress in their field of in-
terest. Access to full articles should be im-
proved by resource sharing networks, regional
interlibrary loans (photocopies) services and
library manpower training.

Pan American Health Organization

The NLM continues to work with PAHO and
especially with the PAHO Regional Library of
Medicine (BIREME) in Sao Paulo, Brazil.

The Library's Assistant Director for Interna-
tional Programs, a member of the Scientific
Advisory Committee for BIREME, will partici-
pate in the 1983 meeting of this committee.
BIREME is unique in the world as a regional
resource. It provides library services and com-
puter-based bibliographic services from the
subset of the MEDLINE data base, trains Latin
American librarians, and has produced a Latin
American Index Medicus.

International Council of Scientific Unions
Abstracting Board

The Assistant Director for International Pro-
grams and the Deputy Director, as the NLM
representative and alternate, respectively, to
the International Council of Scientific Unions
Abstracting Board, attended the annual meeting
of the board. The board consists of information
organizations from a number of countries. Topics
discussed included collaborative undertakings,
status of document delivery in various regions
including the proposals of the Commission of the
European Communities, working groups in vari-
ous subjects, copyright, and an examination of
the future role of the board in international,
scientific, and technical activities.

Visitors and Specialized Training

The NLM continues to receive international
visitors, as well as specialized delegations, who
represented approximately S't countries during
FY 1982. Formal delegations were concerned
with international communications, library man-
agement and resources, information systems
management, and the impact of technology.

Chapter VHI
National Institute on Aging

Introduction

By the end of the century, the total number of
people in the world aged 60 and over will have
doubled. Between 1975 and 2000, the number of
aged in industrialized nations will increase 39
percent; for developing countries, the increase in
this population will be 100 percent.

Although aging in itself is not a disease, the
infirmities that accompany it must be examined
and understood in order to extend the healthy
and productive years, not simply to extend life
itself. Although the relatively new fields of
gerontology and geriatrics are developing rap-
idly, substantive collaboration across borders and
seas is just beginning to emerge.

In May 1974, the United States National In-
stitute on Aging (NIA) was created to support
and conduct biomedical, social, and behavioral
research and training related to the aging proc-
ess and to the diseases and other special prob-
lems of the aged. The Institute has extended its
influence beyond national boundaries, demon-
strating an interest in collaborating with the
international scientific community and with
multinational organizations, as reported in the
sections that follow.

Summary of International Programs
and Activities

Activities With the World Heahh Organization

NIA's association with WHO began during the
initial years of the Institute's existence. The
relationship was formalized in 1980 when the
NIA was designated as the first WHO Collabo-
rating Center for Joint Cooperation on Research
on the Care of the Aged. Over the years, the
NIA Director and other staff members have
served as advisors to the WHO Global Program
on the Care of the Aged. During FY 1982, mem-
bers of the Institute's staff have participated in
a number of WHO-sponsored events.

In October 1981, the NIA Director took part in
a presentation titled "Research in Gerontology"
before the WHO Global Advisory Committee on
Medical Research (GACMR). On the basis of that
meeting the committee recommended that a
WHO group be convened to plan future cross-

national epidemiological and social-survey re-
search on the elderly and that a second WHO
group be established to develop a program on
senile dementia, because "a concentration of
ideas, techniques, and research workers" now
exists, as observed by the GACMR. The Group on
Senile Dementia met in April 1982 and proposed
seven areas of reseach for consideration: points
of possible intervention in neurosynoptic trans-
mission and neuropeptides; low viruses and pri-
ons; genetic susceptibility; autoimmunity; trace
metals; noninvasive studies of cerebral metabo-
lism, including positron emission tomography;
and neural membrane studies. The Institute will
meet in January 1983. In both instances, the
WHO Global Program on Care of the Aged is
expected to develop worldwide networks of
collaborating institutions.

Also in connection with this meeting, the NIA
updated an analysis of participating institutes
and various national programs to provide a bet-
ter understanding of their goals, priorities, or-
ganizational structures, and activities. Overall,
the analysis reveals that nations with widely
differing political, cultural, economic, and social
settings recognize the need for gerontologically
related research and that this recognition often
is in response to the growing number of older
people in their own population. The WHO has
viewed this effort as a basis for collegiate col-
laboration between the institutes described in
the profiles. The network is open-ended, and
other institutes are welcome to take initiatives
for research collaboration, either collectively
with the network or individually with an insti-
tute. Copies of "Profiles of National Research
Institutes and Programs on Aging" are being
transmitted by WHO to organizations concerned
with aging listed in United Nations documents
and by the International Federation on Aging to
all its national member organizations. Interested
individuals may obtain a copy from the Inter-
national Coordinator, National Institute on
Aging, Building 31, Room 2C07, National
Institutes of Health, Bethesda, Maryland 20205.

Extramural Programs

The Institute's Biomedical Research and
Clinical Medicine Program currently supports
basic and clinical research through grants to five

investigators outside the United States (in Can-
ada, Belgium, and Israel). Three of the projects
deal with molecular and cellular biology, one
with immunology, and one with the clinical path-
ology of Alzheimer's disease.

The project on Alzheimer's disease is being
conducted by an investigator at the University of
Western Ontario. It is designed to determine the
relationship between pathological and clinical
measurements of Alzheimer's disease using
clinical, neurophysiological, biochemical, his-
topathological, and radiographic characteristics
of a well-defined clinical population. Results
obtained during the first year of the grant in-
dicate that viable synaptosomes (preparations of
presynaptic nerve endings) suitable for neuro-
chemical or neuropharmacological studies can be
prepared if brain tissue is obtained within ap-
proximately 8 hours after death. The synapto-
somes will be used to provide data related to the
disease process in patients afflicted with Al-
zheimer's disease, particularly with regard to
neurotransmitter function.

Although the Behavioral Sciences Research
Program of the Institute does not support in-
vestigators from outside the United States di-
rectly, it does support six domestic grants with
foreign components. These are primarily cross-
cultural and cross-national comparative studies
related to such areas as aging and support sys-
tems, community influence, retirement levels,
and economic analyses involving specific popu-
lations such as those found in Hong Kong, the
U.S.S.R., Israel, and Eastern European countries.

aging. Of the ^0 national reports submitted, the
NIA provided the section on Research and Train-
ing of the U.S. National Report.

The developing countries' recognition that
they will experience dramatic changes in age
composition was a primary achievement of the
assembly. The International Plan of Action calls
for the Center for Social Development and Hu-
manitarian Affairs in Vienna to serve as the U.N.
focal point and coordinator for aging and to
follow up on the objectives of the UNWAA.

Other international workshops and conferences
in which Institute staff participated during FY
1982 are listed below.

• WHO Workshop on Information Transfer
in Mental Health

• Planning Meeting for the WHO Confer-
ence on Self-Care/Health Promotion
Among the Elderly (to be held in 1983)

• WHO Workshop on Health Planning for
the Elderly

• Special Meeting of the National Acade-
my of Medicine of Mexico Concerning
the Needs of the Elderly

• International Congress on Aging and
Environmental Factors

• International Conference on Life-Course
Research on Human Development

International Conferences, Seminars,
and Meetings

• European Society of Neurochemistry

• International Congress on Neuropathology

The United Nations World Assembly on Aging
(UNWAA) was held at the Hofberg Palace in
Vienna, Austria, from July 26 to August 6, 1982.
It was convened to address issues pertaining to
worldwide population changes caused by declin-
ing mortality, fertility, and migration. Numerous
preparatory meetings, beginning as early as
1979, were held around the world.

The NIA contributed to the assembly in two
capacities— as a member of the United States
Federal Interagency Committee on Aging for the
UNWAA and as a WHO collaborator. The NIA
Director participated in the assembly as an
advisor to the WHO delegation. WHO, as a
specialized agency of the United Nations, pre-
sented a "Technical Discussion Paper on the
Health Policy Aspects of Aging," which was
largely derived from the NIA-supported WHO
Preparatory Conference for the UNWAA held in
Mexico City in December 1980.

Health and nutrition were dominant issues in
the assembly's International Plan of Action, a
plan that gives high priority to research on the
developmental and humanitarian aspects of

• Fifth International Symposium on Car-
diology and Aging

• Third International Erwin Riesch Sympo-
sium on Cardiac Adaptation to Hemo-
dynamic Overload Training and Stress

• Tenth International Meeting of the In-
ternational Society for Social Geron-
tology

• Chemical Institute of Canada's 65th
Canadian Chemical Conference and
Exhibition

• Thirteenth Collegium Internationale
Neuro-Psychopharmacologicum Congress

• Meeting in France to Consult on Policies
Concerning Research and Aging in France

• WHO/Serono Symposia on Role of Basic
and Applied Research in Achieving
Health for All by the Year 2000

• International Conference on Aging of the
Brain

• Tenth Aharon Katz-Katchalsky Con-
ference

• Meeting with the WHO Collaborating
Center on Health and Psychosocial
Factors

• International Symposium on the Aging
Brain

Intramural Programs and Activities

The majority of the Institute's intramural
research on aging is conducted at the Gerontol-
ogy Research Center in Baltimore, Maryland. In
FY 1982, information and research results were
exchanged with visitors from 13 countries: Aus-
tralia, Brazil, Canada, China, the Democratic
Republic of Germany, France, the United King-
dom, Italy, 3apan, Sweden, Switzerland, Thai-
land, and Yugoslavia.

The Human Performance Section of the Clin-
ical Physiology Branch has two projects involving
scientific exchange at the international level.
Sample populations of normal Guamanians
(Chamorros) and of Guamanians afflicted with
amyotrophic lateral sclerosis/Parkinsonism de-
mentia complex are utilized in collaboration
with 3apan for cross-sectional and longitudinal
evaluation of bone loss in a study related to
osteoarthritis and bone loss, which are age-
related changes of the human skeleton that may
result in incapacity.

The second study on normal human variance
involves a continuing collaborative effort with
WHO and other national and international bio-
logical laboratories located in France, New
Guinea, Greece, New Zealand, India, and Aus-
tralia for the purpose of coordinating the col-

lection, evaluation, and interpretation of der-
matoglyphic data. The objectives of this project
include the study of dermatoglyphics as it re-
lates to aging, to distribution among human
populations, and to genetics; and as it functions
as a disease marker.

Thus far, the study has revealed significant
differences in the digital pattern frequencies of
patients with breast cancer, individuals with high
risk for developing breast cancer, and non-
affected controls.

NIH Visiting Program and Health Scientist
Exchange Programs

The NIA intramural program continues to
enjoy active Visiting Program participation.
During FY 1982, 3^^ scientists from 16 coun-
tries—Australia, Canada, Chile, Egypt, Finland,
France, Hungary, India, Israel, Italy, Japan,
Poland, Sri Lanka, Sweden, Turkey, and the
U.S.S.R.—received research training in the lab-
oratories at the NIA Gerontology Research Cen-
ter in Baltimore.

The areas of research in which guest workers
participated include pathophysiological and
hormonal regulation of membrane transport
systems; alteration of kidney membrane-bound
enzymes in aging rats; studies on the relation-
ships of cerebral metabolism to brain function
and aging, the blood-brain barrier and central
nervous system function, and transport systems
active at the blood-brain barrier; drugs poten-
tially useful for diseases prominent in sene-
scence; the role of cell membrane structure on
cellular recognition; a survey of the immune
function of participants in the Baltimore Longi-
tudinal Study of Aging; and learned modification
of visceral function in man. In summary. Visiting
Program participants contributed to 16 of 60
NIA intramural projects.

Chapter IX
National Institute of Allergy and Infectious Diseases

Introduction

The National Institute of Allergy and Infec-
tious Diseases (NIAID) was formally established
by law in 1948 as the National Microbiological
Institute. Its name change in 1955 reflects a
heightened emphasis on research in communi-
cable diseases and immunological disorders. The
NIAID assumed primary responsibility for ac-
tivities in tropical medicine at the NIH in 1968
when the NIH Office of International Research
was disbanded. In 1979, the Office of Recombi-
nant DNA Activities was assigned to the NIAID.

Approximately 600 staff members at Bethes-
da, Maryland, and at the Rocky Mountain facil-
ities in Hamilton, Montana, carry out NIAID in-
tramural research while the extramural research
program is implemented through research or
training grants and contracts awarded to aca-
demic and research institutions. In FY 1982,
tropical medicine and international research
accounted for 73 percent of the extramural
budget.

In industrialized societies patients seek medi-
cal attention for infectious diseases more fre-
quently than for any other disorder. In develop-
ing countries, these diseases are the leading
cause of reported morbidity and mortality. Thus,
advances in the domestic NIAID program have
inherent and far-reaching relevance for national
health authorities outside the United States and
for agencies that cooperate with them in apply-
ing new knowledge and technology to disease
prevention and control.

During FY 1982 the NIAID continued to assign
special priority in its Tropical Medicine Program
to filariasis, leishmaniasis, leprosy, malaria,
schistosomiasis, and trypanosomiasis~the six
diseases targeted for intensive research by the
World Bank/UNDP/WHO Special Program for
Research and Training in Tropical Disease
(TDR). Priority placement on the six diseases
also occurs through the NIAID International Co-
operation in Infectious Diseases Research
(ICIDR) Programs and through the Tropical Dis-
ease Research Units (TDRU's). Research prog-
ress on each of these tropical diseases is re-
ported separately to facilitate communication
and coordination with WHO and other interna-
tional agencies that constitute a global network
on research in tropical diseases.

The NIAID Tropical Medicine Program also
addresses other issues for which international
collaboration is essential to complement the
domestic research effort, including general
parasitology; tropical bacteriology, mycology,
and virology; rickettsioses; and vector patho-
gens. Infectious diseases that constitute more
serious public health problems in developing
countries than in the United States are not in-
cluded in NIAID's reporting of its Tropical Med-
icine Program because the majority of these
conditions are covered in NIAID domestic pro-
grams. Examples include gastroenteritis other
than cholera, hepatitis, acute respiratory ill-
nesses, and sexually transmitted diseases. Thus,
in addition to the NIAID Tropical Medicine Pro-
gram, the bulk of which is carried out in the
United States, this report also summarizes
NIAID international activities in all disease
areas.

General parasitology consists of research on
parasites of importance to human health other
than those covered by the TDR Program. In-
cluded are awards for basic research projects,
parasitology research training, and career de-
velopment awards that are not easily categor-
ized specifically for any one of the targeted
TDR diseases. The NIAID regards basic research
in parasitology as a prerequisite to further ad-
vancements in the prevention or control of all
six parasitic diseases of TDR. Indeed, the PHS,
Army, Navy, U.S. Agency for International De-
velopment (US AID), and WHO disease-oriented
initiatives have evolved from breakthroughs in
basis research and will continue to rely on them
to achieve their goals of vaccine and drug de-
velopment or vector control.

The rickettsial program, representing 6 per-
cent of NIAID activity, is directed primarily
toward Rocky Mountain spotted fever. Tropical
bacteriology awards (7 percent) focus on cholera
and related organisms, tuberculosis and myco-
bacteria other than leprosy, and, to a lesser de-
gree, spirochetes, plague, and yersinia. Although
WHO has recently established a global Diarrheal
Diseases Control Program with a major research
component in epidemiology, improved drugs, and
vaccine development, NIAID activities in viral
and bacterial diarrheas (other than cholera), as
indicated, are included in the regular program
and hence are not part of the Tropical Medicine
Program. Histoplasmosis and coccidioidomycosis

research (l.'f percent) constitutes the bulk of
activities in tropical mycology.

Tropical virology {7A percent) concentrates
research projects on arboviruses, rabies, and
other viral agents of public health importance
(e.g., Lassa fever) that are not endemic to the
United States. Vector pathogen activities (6.3
percent), by contrast, consisted of 26 projects,
10 on mosquito studies and others on tick, mite,
and snail vectors of human viral, rickettsial, and
trematode diseases.

The three major categories of NIAID support
for Tropical Medicine and International Health
are intramural research, domestic extramural
research, and competing foreign awards. Foreign
investigators are eligible to compete with U.S.
investigators for NIAID grants and, under special
conditions, for contract funds. Most NIAID-
sponsored international research, however, is
generated through NIH awards to U.S.-based
scientists and institutions. Approximately 70
percent of the awards are for extramural grants
or contracts to U.S. investigators or institutions.
Awards to non-U. S. scientists or institutions
represent 3 percent of the total Tropical Medi-
cine and International Research budget.

NIAID grants for ICIDR are intended to pro-
vide linkages for research conducted outside the
United States. The ICIDR Program, as well as
the NIAID-supported Tropical Disease Research
Units within the United States, is discussed in
more detail under bilateral activities. Additional
award mechanisms include bilateral medical re-
search programs and the Special Foreign Cur-
rency (P.L. i^ZO) Program, which involves six
countries and is coordinated by the Fogarty In-
ternational Center for the NIH. In FY 1982 the
NIAID was most actively involved with Argen-
tina, Australia, Brazil, China, Colombia, Costa
Rica, the Dominican Republic, Egypt, France,
Gambia, Ghana, India, Indonesia, Israel, 3apan,
Kuwait, Mexico, the Netherlands, Nigeria, Pak-
istan, Panama, Poland, Sierra Leone, Sudan,
Sweden, Switzerland, Thailand, Trinidad and To-
bago, the United Kingdom, and Venezuela.

Going beyond the major award categories de-
scribed above, the full extent of NIAID support
for international health includes the overseas
components of intramural or domestic extra-
mural awards outside the diseases classified un-
der the rubric of tropical medicine.

Summary of Interaational Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

The NIAID conducts scientific exchange and
collaborative research through a variety of

mechanisms that extend from informal direct
contact between investigators to formal agree-
ments for cooperation between the United States
and other governments. Because of its research
responsibilities in tropical diseases, microbiol-
ogy, and vaccine development, the NIAID has a
particular need to foster cooperation with sci-
entists and institutions in developing countries.
In recent years, formal bilateral science and
technology agreements with developing countries
have proliferated, encouraging a tendency for
these bilateral programs to move into additional
areas such as immunology and genetic engi-
neering.

Argentina

Long-standing collaboration with the Institute
Fatala Chaban (Buenos Aires) on the cell biology
of Trypanosoma cruzi strains and single cell
isolate clones has been maintained.

Australia

Formal collaboration was begun between t'le
NIAID and the Fairfield Hospital (Melbourne) on
the biology of the hepatitis A virus. Collabora-
tion was also initiated between the NIAID and
the Australian National University. Research
here will focus on the biology of mousepox virus
and development of a simple, sensitive, and
specific in vitro test for ectromelia virus to
control and prevent this disease, which has re-
cently produced epizootics at the NIH and rep-
resents a serious threat to U.S. biomedical
research.

At present the NIAID extramural program
supports five Australian investigators at the
Walter and Eliza Hall Institute of Medical Re-
search (Melbourne). In addition to ongoing sup-
port for research on mechanisms of lymphocyte-
antigen interactions, recent awards support the
use of animal models for the development of
vaccines against parasites, cell surface moni-
toring by recirculating lymphocytes, investi-
gation of T cell development in the thymus, and
analysis of T hybrid mas with defined idiotypes.

Bangladesh

Collaborative research in Bangladesh has fo-
cused on the Cholera Research Laboratory (CRL)
in Dhaka. This productive relationship is chron-
icled in Cholera; The American Scientific En -
counter by Seal and van Heyningan, which will be
published in early 1983. The NIAID collaborates
with the International Center for Diarrheal
Disease Research/Bangladesh (ICDDR/B) for
longitudinal studies of viral gastroenteritis in
infants and young children. (This research labor-
atory was designated as the ICDDR/B in 1978
and functions as a multilateral research insti-
tute.) NIAID awardees in enteric diseases at

Harvard, 3ohns Hopkins, Maryland, and Wash-
ington Universities continue to collaborate with
ICDDR/B. In February 1982, NIAID staff visited
ICDDR/B to identify additional areas for sci-
entific exchange and collaboration.

Belgium

The NIAID continues collaboration with sev-
eral Belgian scientists on the ontogeny and dif-
ferentiation of cells of the rabbit immune sys-
tem. The Director, Institut de Medicine Tropical
(IMT) Prince Leopold (Antwerp), visited the
NIAID early in 1982 to discuss development of a
joint research effort directly between the NIAID
and IMT, which would include joint activities in
developing countries.

Bolivia

The NIAID is exploring the possibility of col-
laborative activities in Chagas' disease and
leishmaniasis with the Centro Nacional de En-
fermedades Tropicales in Santa Cruz. Discus-
sions were also held with the Institute of High
Altitude Biology in La Paz on mutual interests
related to effects of altitude and internal migra-
tion on patterns of communicable diseases.

Brazil

Through a number of activities in Brazil, the
NIAID has developed strong institutional ties.
Efforts are now underway between the Fundacao
Oswald© Cruz (FIOCRUZ) and the NIAID to de-
velop a joint work plan in tropical medicine.

In its intramural program, the NIAID has of-
fered research training and bench facilities to
Brazilian scientists for many years. Active col-
laboration continues with scientists at the Uni-
versity of Goias on the pathogenesis of leish-
manial and T. cruzi infections. During FY 1982
an NIAID Visiting Scientist spent 8 months at the
University of Boias in cooperation with WHO to
study Chagas' disease. Four of the 10 ICIDR
awards made in FY 1982 to U.S. investigators
are for collaborative studies in BraziL Cornell
University Medical College collaborated with the
University of Bahia on Chagas' disease and the
endemic forms of cutaneous, mucocutaneous,
and visceral leishmaniasis. The Harvard School
of Public Health currently in its second ICIDR
Program project, is collaborating with the Uni-
versity of Bahia and FIOCRUZ in Rio de Janeiro
on Chagas' disease and schistosomiasis.

FIOCRUZ is also involved in a University of
South Florida ICIDR exploratory grant on the
spread of schistosomiasis in newly developed
agricultural colonies in the northeast (Piaiu) and
in settlement areas along the Trans-Amazon
Highway. Columbia University participates in
collaborative research with the Federal Univer-
sity of Rio de Janeiro in which lectins are being

used to study cell surface carbohydrates of viru-
lent and avirulent forms of Leishmania .

The Cornell on-site coordination for lab and
field studies is based at the FIOCRUZ laboratory
in Brotas, where major responsibility is building
and maintaining a small animal colony. Most of
the work at the FIOCRUZ is concerned with the
immunology and biochemistry of leishmaniasis.

At the Professor Edgard Santos Hospital,
Bahia University investigators are exploring the
genetics and clinical aspects of American vis-
ceral leishmaniasis (AVL or kala-azar). Carefully
designed, the genetic studies of AVL should yield
definitive results on whether a genetic risk fac-
tor is associated with AVL. The immune studies
are concerned with lymphocyte transformation,
suppressor cell concentration, and T helper and B
cell activity. Also in process are field studies in
Jacobina on AVL, a prospective longitudinal field
study of AVL that has already provided new in-
sights into the natural history of the disease, and
studies of cutaneous and mucocutaneous leish-
maniasis in Tres Bracos.

At the Federal University of Bahia, the lab-
oratory, which is managed by a Harvard immu-
noparasitologist who established the ELISA test
for serological identification of Chagas' disease,
U.S. and Brazilian collaborators are hoping to
develop an ELISA test for detecting circulating
T. cruzi antigen to circumvent xenodiagnosis, a
cumbersome and slow diagnostic technique that
requires weeks instead of hours for results. Mon-
oclonals and their corresponding antibodies de-
veloped at Harvard will be used to identify
strains of T. cruzi collected in different parts of
Latin America.

The Professor Edgard Santos Hospital, which
houses a cardiology unit directed by the ICIDR's
Brazilian collaborator, is engaged in a classical
study of Chagas' cardiomyopathy. Field studies
on Chagas' disease are planned and coordinated
by a Brazilian epidemiologist trained at Harvard.
Entomological studies stemming from colla-
boration between the on-site coordinator and
FIOCRUZ provide valuable information to con-
trol units working in the study area.

Canada

NIAID scientists are collaborating with the
University of Western Ontario on the genetic
control and mapping of endogenous proviruses.
During FY 1982, a new NIAID grant was awarded
to the Montreal General Hospital for study of
INR gene-complex probes in host-parasite inter-
actions. A second award at the University of
Manitoba concerns the suppression of the IgE
response.

China

The U.S.-P.R.C. Joint Committee on Science
and Technology in Medicine and Public Health

held its first meeting in Beijing in June 1979.
The NIAID was assigned lead responsibility for
immunology and secondary responsibility with
the Centers for Disease Control (CDC) in para-
sitology and infectious diseases. The parasitic
and infectious diseases emphasized in the bilat-
eral health protocol are malaria, schistosomiasis,
hepatitis, and influenza. The NIAID subsequently
assumed the lead role in recombinant DNA re-
search within the Immunology Protocol.

As a result of the exchange visits of the U.S.
and Chinese coordinators, the protocol for co-
operation in immunology was modified for FY
1981-82 to include the immunology of infectious
and parasitic diseases; cancer; diseases of the
immune system, including primary immune defi-
ciency diseases; autoimmunity and allergy; and
skin and organ transplantation. The research
approaches will involve immunobiology, immuno-
genetics, molecular immunology, immunopharm-
acology, and clinical immunology. The Immunol-
ogy Work Plan provides for scientific exchange,
research training, working groups, and collab-
orative research in immunogenetics and clinical
immunology. The U.S.-P.R.C. Joint Committee
endorsed these modifications at its second meet-
ing in the fall of 1982. The third meeting is
scheduled for FY 1983 in Bethesda.

By mutual consent, the highest priority in the
Immunology Protocol is to enhance the research
training opportunities for promising younger
Chinese scientists at leading U.S. institutions.
The Chinese Government, WHO, and private
foundations have been very active in this area
with U.S. universities outside the U.S.-P.R.C.
Joint Committee and with minimal NIAID in-
volvement. The Joint Committee has been an
effective catalyst for research training and co-
operative research at the NIH and other Federal
agencies. In May 1982, U.S. scientists visited the
University of Beijing and the Institute of Basic
Medical Sciences, under the Immunology Proto-
col. An NIAID scientist was one of three U.S.
scientists who participated in a workshop, "Bio-
chemistry of Schistosomiasis," in Shanghai in
September 1982; an NIAID grantee at the Acad-
emy of Natural Sciences (Philadelphia) traveled
to China to study the distribution and ecology of
snail vectors of schistosomiasis in Malaysia and
Thailand.

In FY 1982 NIAID signed a 2-year interagency
agreement with CDC to share costs on a collab-
orative protocol with the Institute of Virology
(Beijing) and Shanghai First Medical College to
study the efficacy of the NIH inactivated hepa-
titis B antigen (HBsAg) carrier mothers. Vac-
cines that were previously studied in Chinese
adult volunteers are now being provided to in-
fants born to HBsAg carrier mothers in Beijing
and Shanghai.

The NIAID also supported the participation of
U.S. scientists in a workshop entitled "Origin of
Pandemic Influenza Viruses."

Colombia

After 20 years of NIAID support for the In-
ternational Center for Medical Research (ICMR)
in Call, scientists at Tulane University have
proposed collaborative research with the Colom-
bian Fund for Research (COLCIENCIAS) under
the ICIDR mechanism. Now in its second year,
the research emphasizes both epidemiological
and basic biological investigations of selected
vector-borne diseases, especially filariasis and
trypanosomiasis. The ELISA test is being used
for serological testing of patients from endemic
areas with W. bancrofti . Strains of T. cruzi and
T. rangeli have been cloned and will be reeval-
uated biologically and for isoenzyme characters
prior to large-scale production of stage-specific
antigens.

As the Tulane-COLCIENCIAS ICIDR builds on
long-standing ICMR collaboration, joint publi-
cations in refereed journals are already begin-
ning to appear. Field studies along the Colom-
bian bank of the Amazon demonstrated an
average prevalence of mansonellosis in teen-
aged and adult Amerindians of ^7 percent (range
16-85 percent). Entomological studies confirmed
studies in Brazil that Simulium amazonicum and
S. argentiscutum serve as intermediate vectors
and confirmed conclusively for the first time in
South America that culicine mosquitoes ( C.
insinuatus) can serve as vectors. Similar studies
confirmed the presence of Dipetalonema pers -
tans in the Colombian Amazon (Guainia) and that
its prevalence (10.6 percent) and distribution
may be far greater than previously suspected.

Costa Rica

For 7 years, the NIAID has supported epidem-
iological studies of viral hepatitis by U.S. and
Costa Rican scientists associated with Louisiana
State University. In FY 1982, the team reported
on a prospective investigation of the spread of
hepatitis A virus (HAV) within households in two
rural areas in Costa Rica. The initial prevalence
of anti-HAV antibody was 26 percent in children
and 71 percent in adults. Overall, 70-83 percent
of antibody negative contacts acquired HAV in-
fection. In contrast to observations in the United
States, almost all "susceptible" adults developed
inapparent infection while the clinical/silent
case ratio in children was 1.8/1. The absence of
IgM in older people suggests that antibody con-
version in many Costa Rican adults represents
reinfection and restimulation of IgG rather than
new disease.

Denmark

In October 1981, the Deputy Director General
of the National Board of Health visited the
NIAID.

Dominican Republic

Finland

The University of Arizona collaborative
studies between the NIAID and the Instituto
Dermatologico (Santo Domingo) continue. The
studies are significant because this focus on
leishmaniasis in the Dominican Republic is the
only documented concentrated attention on this
disease in the Caribbean proper. This study has
demonstrated a uniquely high incidence of dif-
fuse cutaneous leishmaniasis, a rare manifesta-
tion previously reported in Ethiopia and Vene-
zuela.

The University of South Florida is supported
through the NIAID regular grants program to
study filariasis in the Dominican Republic.

Ecuador

In April 1982, the Chief, National Planning
Division, Ministry of Public Health, visited the
NIAID under the auspices of the Eisenhower Ex-
change Fellowship Program.

Egypt

The NIAID has been involved in collaborative
research with Egyptian investigators for more
than a decade, most recently under the terms of
the U.S.-Egypt Agreement for Collaboration in
the Areas of Science and Technology. Collab-
orative projects funded by the Special Foreign
Currency (P.L. li&O) Program were the following:
(I) Taxonomy of Genus Bulinus, (2) Bionomics of
Anopheline Vectors of Malaria, (3) Ticks and
Tickborne Diseases of the World, and W Epi-
demiology of Bancroftian Filariasis.

The NIAID is involved in collaborative efforts
with CDC-administered P.L. 480 projects. The
Laboratory of Infectious Diseases and the
NIAID-funded Infectious Enteric Diseases Study
Center at the University of Texas (Houston)
provide virologic and bacterial support respec-
tively to the Diarrheal Diseases Project at the
Epidemiology Study Center in Bilbais.

The NIAID contract with the Research and
Training Center on Vectors of Disease (Ain
Shams University) to produce a study entitled
"Epidemiology and Control of Vector-Borne
Diseases in Egypt," a USAID-funded project ad-
ministered by the NIAID, began in December
1981. Cooperating Egyptian institutions in FY
1982 included the Ministries of Health and
Agriculture; El Azhar, Canal, and Cairo Univer-
sities; and the High Institute of Public Health
(Alexandria). Participating U.S. institutions in-
cluded NAMRU-3, Walter Reed Army Institute
of Research, CDC, Cornell, Harvard, Michigan
State, and Yale. The first year activities con-
centrated heavily on the development of re-
search projects in Rift Valley fever, leishmani-
asis, malaria, and medical entomology.

In FY 1982 the NIAID extended its contract
with the Central Public Health Laboratory to
provide foUowup studies of children immunized
with meningococcal type A vaccine from 197'f to
1978. The original contract resulted from a 1973
request from the Finnish National Board of
Health for assistance in dealing with an epidemic
of that disease. The new contract includes eval-
uation of the response to Hemophilus influenza ,
type B vaccine administered as a control in the
197^^ efficacy trials. The recently signed Memo-
randum of Understanding between the DHHS and
the Ministry of Social Affairs and Health pro-
vides for the development and testing of vac-
cines. The DHHS has proposed that the director
of the NIAID Microbiology and Infectious Dis-
eases Program serve as the U.S. coordinator in
this program area.

France

During FY 1982 the NIAID continued its 21
years of support to a Nobel laureate for his work
on skin grafts and surface leukocyte antigens.
The Institut Pasteur began work on a new NIAID
grant to study mechanisms of antigenic variation
in T. equiperdum . NIAID intramural scientists
also collaborated with this institute on genetic
studies of immunoglobulins and other serum
proteins, with the CNRS on the structure and
activity of immunologically important cells and
proteins, and with the Faculty of Medicine/Brest
on tickborne disease agents. In FY 1982 the
NIAID initiated collaborative work for basic
studies on mycoplasmas and related wall-free
prokaryocytes. Collaboration was also begun
with the Hospital Cochin (Paris) on the structure
and function of endogenous murine C type viral
products. In September 1982, the Director,
NIAID, visited INSERM and the Institut Pasteur
to discuss opportunities for more extended
Franco-American collaboration in immunology,
microbiology, epidemiology, and clinical in-
vestigation.

Gambia

The NIAID and NCI initiated discussions this
year with the Medical Research Laboratories
(Banjul) on the feasibility of cooperative epi-
demiologic studies on the efficacy of hepatitis B
vaccine in preventing disease, duration of im-
munity, and prevention of hepato cellular car-
cinoma. NIAID intramural scientists and New
York University staff spent several weeks in
Gambia under USAID and WHO support to con-
duct field trials on the application of radio-
immunoassay, using hybridomas to P. falciparum
in the determination of sporozoite infection
rates in Anopheles gambiae mosquitoes, a sig-
nificant development in malaria research.

Democratic Republic of Germany

A new intramural project was initiated in
collaboration with the Academy of Science
(3ena) on the molecular and genetic analysis of
plasmid-mediated properties among streptococci.

Federal Republic of Germany

Collaboration between the NIAID and the
University of Munich on the systemics and vec-
tor relationships of parasitic arthropods con-
tinued. Grant support was also provided to the
Max Planck Institute for Biology on the poly-
morphism of the major histocompatibility com-
plex.

Ghana

During FY 1982, NIAID intramural staff made
a short trip to the Onchocerciasis Hospital in
Tamale, supported through P.L. 480 funds. A
protocol was developed and arrangements made
for a hospital researcher and an NIAID medical
staff fellow to collaborate in Ghana under a TDR
grant to initiate clinical and immunologic studies
of the reactions (Mazzotti) that occur after
treatment of patients with diethylcarbamazine.

Haiti

The Tulane ICIDR Program continues its col-
laborative project on the epidemiology of filarial
infection in Haiti, with the Institut Francais
d'Haiti. In November 1981 the Association of
Medical Microbiology Chairmen met in Port-au-
Prince, providing NIAID senior staff an oppor-
tunity to meet with USAID country health staff.

India

Since 1962 the NIAID has participated in col-
laborative research with Indian investigators,
largely through P.L. ^^80 Program funding. In
December 1981 the Indian-U.S. Working Group
on Health of the 3oint Science and Technology
Committee met in New Delhi to review and re-
define priority diseases for collaborative re-
search. Mutually agreed-upon areas for emphasis
were acute respiratory diseases, diarrheal dis-
eases, filariasis, guinea worm, hepatitis, Japan-
ese encephalitis, leprosy, malaria, recombinant
DNA technology, rheumatic fever and sequelae,
and tuberculosis. The NIAID reviewed the status
of these activities with the Indian Council of
Medical Research staff in New Delhi in March
1982 and in Washington later in the year with the
Secretary of the Ministry of Health and Family
Welfare.

In 3uly 1982 President Reagan and Prime
Minister Gandhi met in Washington and agreed to

establish a Joint Indo-U.S. Senior Scientific
Panel to consider research areas of priority to
both countries. Biomedical research on leprosy,
immunology, and prevention of blindness were
identified as the three program areas in health.
This initiative will begin in FY 1983.

A new area of cooperation to which the ICMR
gives high priority is acute respiratory diseases,
which are major causes of morbidity and mor-
tality in Indian children.

Collaboration continues among the NIAID, the
Tuberculosis Research Center (Madras), and the
Madras Medical College on the immunology of
filarial infections and the pathogenesis of tro-
pical eosinophilia and lymphangiitis. Current
studies under the project include (1) evaluation
of the pathogenetic significance of blocking an-
tibodies that regulate immediate hypersensi-
tivity responses in patients with filariasis, (2)
determination of the mechanisms responsible for
the control of allergic responses to the parasite,
(3) comparison of the IgE regulatory mechanisms
in patients with filariasis and other allergic
disorders, (4) definition of the IgE as opposed to
the IgG response of patients with filariasis to
other specific antigens, (5) production of mono-
clonal antibodies to filarial antigens for use in
the development of immunodiagnostic or pro-
tective immune reagents and, (6) chemothera-
peutic studies of optimal drug regimens for this
difficult-to-manage disease.

The NIAID continues collaborative studies at
the National Institute of Virology (Poona) on the
epidemiology of hepatitis in India. With the ap-
plication of recently developed laboratory tests,
it is now apparent that the 1955-56 massive
water-associated outbreak of hepatitis in Delhi
was neither hepatitis A nor B. Ongoing studies
indicate that non-A, non-B hepatitis is a com-
mon source of epidemic and sporadic hepatitis in
India. NIAID experiments at the NIH have pro-
duced hepatitis in chimpanzees following the
inoculation of infectious Indian material but
have not yet recovered and characterized the
etiologic agent. As epidemic non-A, non-B hep-
atitis is particularly severe during pregnancy,
efforts are now underway to develop a study
with the National Institute of Virology on the
epidemiology of hepatitis of pregnancy and
childhood cirrhosis. During FY 1982 collabora-
tion was extended to include the Postgraduate
Institute of Medical Education and Research
(Chandigarh) and investigators in Srinigar.

Agreement to undertake a new area of coop-
eration—in Japanese encephalitis—was reached
in FY 1982. In 1981 the Government of India
made a policy commitment to eliminate leprosy
as a public health problem by the end of the
century. Indo-U.S. collaboration in leprosy has
been shared within the PHS among the National
Center for Hansen's Disease in Carville, Louis-
iana; NIAID; and CDC. The Central Jalma In-
stitute for Leprosy (Agra) was awarded one of

the first two ITDR Fellows for a year of re-
search training in mycobacteria at the Tubercu-
losis Research Center of the Veterans Admini-
stration Medical Center (Long Beach). Approval
was confirmed for a collaborative P.L. ^&0
project between scientists of Johns Hopkins
University and the Foundation for Medical
Research (Bombay) on the screening of drugs for
activity against leprosy and the detection of
drug resistance.

The University of Hawaii has an ICIDR ex-
ploratory award to collaborate with the Aligarh
Muslim University on the in vitro cultivation of
human malarial parasites isolated in India, the
drug susceptibility of Plasmodium falciparum ,
and the culture of Indian P. vivax strains in
vitro . NIAID intramural scientists visited the
Central Drug Research Institute (Lucknow), and
two collaborative protocols were completed:
"The identification of immunogens and immuno-
suppressive molecules in primate malarias" and
"Studies on immunity to the sexual stages of the
malarial parasite."

Plans for a fixed-site Indo-U.S. Workshop on
Recombinant DNA were modified in favor of a
March visit by a team of four U.S. scientists led
by the Deputy Director of the NIAID. The team
became familiar with leading Indian scientists
and institutions active in this area. Further
activities and followup are expected to be in-
corporated into the new Indo-U.S. Senior Sci-
entific Panel.

In rheumatic fever and streptococcal disease,
efforts are underway between the University of
Tennessee and the ICMR Streptococcal Typing
Center (New Delhi) to study the epidemiology of
group M streptococcal protein in India.

A collaborative project with the All India In-
stitute of Medical Sciences (AIIMS) to adapt the
radioimmunoassay (RIA) technique to the de-
tection of secretory tuberculoprotein has been
developed by two scientists (one, a Nobel laur-
eate) at the Montefiore Medical Center (New
York City). If successful, this effort should fa-
cilitate the definitive diagnosis of primary cen-
tral nervous system and other extrapulmonary
forms of tuberculosis within days rather than the
weeks now required for the culture and identi-
fication of Mycobacterium tuberculosis . The
AIIMS is also in a position to apply the RIA tech-
nique to other health problems and to serve as a
national center in this field.

Indonesia

Representatives of the National Institute for
Health Research and Development (NIHRD)
visited the NIAID in November 1981 to become
familiar with the NIH. In September 1982 an
NIAID scientist made a short site visit to the
USAID-supported Health Training, Research, and
Development Project to examine the biomedical
research subproject of the NIHRD.

Israel

The NIAID contract with the Kuvin Center for
the Study of Infectious and Parasitic Diseases
(Hebrew University) on the "Epidemiology and
Control of Vector-Borne Diseases in Israel" be-
gan operations in December 1981. This USAID-
funded project involves significant collaboration
in medical entomology with Beersheva Univer-
sity of the Negev and focuses heavily on leish-
maniasis research and field studies and on sur-
veillance for leishmaniasis. Rift Valley fever,
and malaria.

During FY 1982 the NIAID supported three
ongoing investigator-initiated grant awards at
the Weizmann Institute for research on bioener-
getics and control of bacterial behavior at Ha-
dassah University Hospital on new approaches to
marrow and organ transplantation and at the
Israel Institute of Technology on the differen-
tiation and activity of mast cells in culture. Ac-
tive collaboration exists between the NIAID and
the Hadassah Medical Center on the character-
ization of surface IgG in the clones of a murine
B cell lymphoma.

Italy

A transmissable hepatitis agent, the delta
agent appears to be defective in that it requires
coinfection with hepatitis B virus for its own
synthesis. The delta agent is endemic in Italy
where it was discovered in 1977. An NIAID sci-
entist is collaborating with Italian investigators
on this unique virological phenomenon. A sci-
entist in Rome also continues his collaboration
with the NIAID on rabbit IgG allotypes.

Japan

The NIAID is currently involved in two Japan-
U.S. initiatives. The first is the U.S.- Japan Co-
operative Medical Science Program (JCMSP),
initiated in January 1965. Under the terms of
this agreement, both countries have undertaken
joint cooperative biomedical research in diseases
of particular importance in Asia. Under P.L. 86-
610 (the International Health Research Act of
1960) the State Department coordinates foreign
relations and policy of the program while DHHS
is responsible for the scientific elements. The
NIAID has been the lead institute within the NIH
and DHHS since 1968. Although the JCMSP
operates as a bilateral program, scientists from
other countries and/or international agencies
often participate. Applications submitted within
the context of this program by U.S. scientists
compete for available funds on the basis of their
scientific merit without a special NIAID budget
set-aside. Japanese scientists, in contrast,
depend on the program to facilitate their funding
proposals.

Currently there are eight panels: leprosy,
tuberculosis, cholera, hepatitis, parasitic dis-
eases (schistosomiasis and filariasis), viral dis-
eases (arboviruses, rabies, rotaviruses), environ-
mental mutagenesis and carcinogenesis, and
malnutrition. These panels meet annually either
in the United States or Japan. The Director,
NIAID, and staff members serve as the Secre-
tariat to the U.S. delegation to the 3CMSP and
to six of the panels.

At the 1982 3CMSP Joint Committee meeting
in Tokyo, the formal review of the Leprosy and
Parasitic Diseases Panels was completed, and
the Tuberculosis and Viral Diseases Panels were
initiated. The committee recommended that the
Leprosy and Parasitic Diseases Panels be con-
tinued and held additional discussions of the
Leprosy, Tuberculosis, and Parasitic Diseases
Panels. Recognizing the common scientific in-
terests of the Leprosy and Tuberculosis Panels,
the committee recommended that these two
panels hold combined meetings beginning in FY
198^. The committee agreed also that the guide-
lines of the Parasitic Diseases Panel should be
reviewed to accommodate new technologies and
changing needs. Preparatory to such action, a
symposium will be held in conjunction with the
July 1983 Joint Committee Meeting in Bethesda.
Experts will be invited to present current sci-
entific reviews for such parasitic diseases as
malaria, leishmaniasis, and trypanosomiasis, in
addition to schistosomiasis and filariasis.

The second U.S. -Japan initiative developed
when the President of the United States and the
Prime Minister of Japan signed the Japan-U.S.
Science and Technology Agreement for Non-
Energy Cooperation in May 1980. This agreement
is separate from, but coordinated with, the
JCMSP. Within this second bilateral program the
NIAID has lead responsibility for three program
areas: immunization (vaccine development), re-
combinant DNA research, and antiviral agents.
At the first meeting of the U.S.- Japan Program
for Cooperation in Science and Technology
(Tokyo, September 1981), both countries agreed
to continue to develop recombinant DNA re-
search activities within the "umbrella" Science
and Technology Program. The technical aspects
of vaccine development and antiviral agents,
however, will remain with the appropriate
JCMSP Panel, with the referral of matters
requiring policy review and decisions to the U.S.
Chairman of the Science and Technology
Program.

JCMSP panel meetings during FY 1982 in-
cluded the following: cholera, virology, hepatitis,
immunology, tuberculosis, leprosy, and parasi-
tology. Meetings held under the auspices of the
U.S.- Japan Non-Energy Science and Technology
Program were limited to a symposium entitled
"The Introduction of DNA into Eukaryocytic
Cells" and a meeting of the Recombinant DNA
Panel.

Outside the two formal bilateral programs,
two NIAID intramural laboratories have ongoing
collaboration with Japanese scientists. One is
actively involved with the University of Tokyo in
the fractionation of lymphoid cell subsets with
lectins that specifically bind to cell surface
glycan differentation markers. The other, the
Rocky Mountain facilities, also maintains col-
laboration with scientists at the National In-
stitutes of Health (Tokyo) on tickborne disease
agents. In addition, the NIAID supports one ex-
tramural award at St. Marianna University on
genetic studies in the Aedes (Finlaya) toRoi
mosquito.

Kenya

During FY 1982 the NIAID initiated a domes-
tic grant to Cornell University to study the
longitudinal effect of treatment of Schistasoma
hematobium on the nutritional status of school
children. Parameters to be followed include
physical fitness and urinary excretion of iron.

Kuwait

The Director of the Immunology, Allergic and
Immunologic Diseases Program (lAIDP) continues
to serve as a consultant to the Ministry of Public
Health in the development of a national allergic
disease program and the construction of an al-
lergy research center.

Mexico

The University of Washington has an explor-
atory ICIDR award for work with the National
Polytechnic Institute (Mexico City) on the ser-
odiagnosis of subclinical leprosy. During the past
year the surface protein of live M. leprae has
been found to consist of five major subunits. A
36,000 dalton subunit common to M. leprae , M.
leprae murium, and BCG may represent a shared
antigen. The NIAID continues association and
collaborative research that began over 10 years
ago with Mexican scientists and the Center for
the Study of Amebiasis (Mexico City). The NIAID
also provided support for U.S. scientists to at-
tend an International Symposium on Immunobi-
ology of Infectious Disease. Approximately 200
Mexican immunologists participated in the sym-
posium. The PHS subsequently convened a meet-
ing at the NIAID to discuss cooperation between
the United States and Mexico on research and
training in communicable diseases. Economic
conditions in Mexico, however, limited followup.

Netherlands

Two intramural laboratories have continuing
collaborative research activities with counter-
parts in the Netherlands: one with the Nether-
lands Red Cross Book Transfusion Service on the

mechanisms of immune recognition of viral an-
tigens and the other with the Catholic University
of the Netherlands on the taxonomy, ecology,
and colonization of parasitic arthropods of med-
ical importance. Two research contracts with
the University of Leiden are concerned with the
acquisition of homozygous typing cells and anti-
sera to HLA-A,B, and C loci and b cells.

Nigeria

Ohio State University has an active ICIDR
exploratory grant with the University of Nsukka
to study the biological control of mosquitoes
that transmit malaria by Bacillus thuringenesis .
A Nigerian Visiting Fellow at the NIAID is car-
rying out investigations on the binding of red
blood cells infected with malaria to the endo-
thelium of blood vessels. The NIAID also par-
ticipated actively in the biomedical research
component of the U.S.-Nigeria Joint Task Force
on Health Cooperation.

Pakistan

Although the University of Maryland Inter-
national Center for Medical Research at the
Pakistan Medical Research Center (Lahore)
terminated in May 1980, the NIAID maintains an
active project with the University of Maryland
on the ecology of mosquitoes in Pakistan and the
genetic control of Anopheles culicifacies , an
important vector of malaria in that country.

Panama

Humboldt Institute") of the Universidad Peruana
Cayetano Heredia, as the national research
center for infectious and tropical diseases. The
NIAID maintains regular contact with the
institute.

Poland

In October 1981 the Chairman of the Coordi-
nating Commission for Polish-American Scien-
tific Collaboration visited the NIAID to discuss
active projects in the Polish-U.S. Agreement on
Cooperation in the Field of Health. At present
there are two active projects with extramural
scientists on the immunochemistry of Shigella
lipopolysaccharides and on the role of macro-
phage surfaces in the regulation of immune
response.

Sierra Leone

The NIAID and FIC completed an interagency
agreement with CDC for studies in rural Sierra
Leone on Mastomys natalensis (a multimammate
mouse) and Lassa fever. The project character-
ized the populations of M. natalensis in and
around villages, determined the relationship of
genetic subpopulations of mice to transmission
of Lassa fever to humans, described the epi-
demiologic and socioeconomic factors associated
with transmission in the village, and developed
strategies to prevent rodent-human transmission.

South Africa

During FY 1982 the NIAID supported the GML
through the Gorgas Memorial Institute (Wash-
ington, D.C.) for investigations in Panama on the
transmission and reservoirs of the St. Louis virus
in tropical ecosystems. The GML also collabo-
rates with the NIAlD-supported Yale Arbovirus
Research Unit on the epidemiology of the yellow
fever virus. Intramurally, the NIAID maintains a
collaborative relationship with the GML on long-
itudinal studies of viral gastroenteritis in infants
and young children.

Papua New Guinea

The NIAID supports entomologists through a
domestic grant to the Bernice P. Bishop Museum
(Hawaii) to collect and characterize larval trom-
biculidae (Acarina) in Papua New Guinea. NIAID
scientists are developing a proposal to carry out
population-based field studies on malaria in
association with the Papua New Guinea Institute
of Medical Research.

Peru

The Ministry of Health has recognized the
Instituto de Medicina Tropical ("Alexander von

The NIAID currently supports a research con-
tract with the State University of New York
(Syracuse), which provides for collaboration with
the Bureau of Biologies (BOB) of the Food and
Drug Administration, the South African Institute
for Medical Research (Johannesburg), and the
University of Cape Town to test the efficacy of
the new BOB meningococcus, type B polysac-
charide vaccine in infants and young children
during the ongoing epidemic of that disease in
South Africa. Safety and efficacy studies had
previously been carried out in U.S. children at
NIAID Vaccine Evaluation Centers at Baylor
University and the University of Vermont. The
NIAID continues a long-standing collaboration
with the Division of Veterinary Services (Onder-
stepoort) on the systematics and vectors of
parasitic arthropods.

Spain

An NIAID scientist was a member of the four-
person U.S. team that assisted the Spanish Gov-
ernment in October 1981 with the investigation,
management, and control of the toxic poisoning
associated with an adulterated batch of com-
mercial olive oil.

The NIAID Associate Director for Interna-
tional Research visited the Ministry of Health
and the Centro Nacional de Microbiologia, Vir-
ologia, e Immunologia Sanitorias (Majadahonda)
to discuss opportunities for participation in the
U.S.-Spain Science and Technology Program.

Sri Lanka

An NIAID scientist visited Sri Lanka in Octo-
ber 1981 in conjunction with a workshop entitled
"Diagnosis, Evaluation, and Control of Lym-
phatic Filariasis."

Sudan

Through an ICIDR Program project award,
Michigan State University is collaborating with
the Ministry of Health on the clinical trials of
new antischistosomal drugs (e.g. oltipraz), the in
vitro cultivation and drug-sensitivity testing of
malarial strains from the Sudan, the ecology of
Simulium damnosum , and the epidemiology of
human onchocerciasis. Collaborative arrange-
ments have been made with the WHO Malaria
Training Center (Sennar), USAID, Rhone Poulenc
(Paris), and West German investigators.

An NIAID scientist visited the Sudan to deter-
mine whether a collaborative study on leish-
maniasis might be feasible and to attend a 1-day
review in Khartoum of the ICIDR project. Col-
laborative investigators gave presentations re-
garding administration of the program and
technical reports on schistosomiasis, onchocer-
ciasis, and malaria.

A recent article in Science reported that sera
collected from individuals living in malarious
regions of the Sudan not only contained mero-
zoite-blocking antibodies but also caused intra-
cellular parasite deterioration and classical
crisis forms in cultures of P. falciparum . This
ICIDR award has also produced 6 additional pa-
pers in press and 12 abstracts of papers present-
ed or about to be presented at national meetings.

Sweden

The NIAID continued discussions with Swedish
health authorities on bilateral epidemiologic
research opportunities in the Stockholm County
Health Care Information System and in the
NIAID/USAID Regional Project entitled "Epi-
demiology and Control of Vector-Borne Diseases
in the Near East." At present, the NIAID and
Swedish intramural scientists are collaborating
in two areas: one with the Universities of Lund
and Uppsala on the molecular aspects of myco-
plasma-eukaryocyte interactions and the other
with the University of Uppsala on the structural
and functional relationships of bacterial antigens
in the immune response.

Switzerland

NIAID intramural scientists are actively col-
laboratng with Swiss investigators at Basle on
the immunology and chemotherapy of systemic
mycoses and at Neuchatel on the natural history
and public health significance of a previously
unrecognized rickettsia in the Ixodes ricinus tick
similar to the Rocky Mountain spotted fever
agent. An investigator-initiated grant to the
University of Zurich supports studies on the in
vitro and in vivo specificity of virus immune T
cells. A new training grant provides research
training at the University of Geneva on the
cloning of murine histocompatibility-2 genes.

Tanzania

The Director of the National Institute of Med-
ical Research (Dar el Salaam) visited the NIAID
in July 1982.

Thailand

The University of Illinois ICIDR Program
project award involves collaboration with the
Universities of Cincinnati, New Mexico, and
Chiang Mai and the McKean Rehabilitation
Institute. It includes four interrelated areas:
epidemiology and seroepidemiology of leprosy
infection and disease, genetic studies of sus-
ceptibility to leprosy, immunoregulatory abnor-
malities and immunopathology of leprosy, and
phagocytic cell functions and metabolism in
leprosy.

Trinidad and Tobago

Rockefeller University has received an NIAID
grant to continue collaborative studies with
Trinidadian investigators on the streptococcal
nephritogenic protein derived from the serum of
patients with acute, post-streptococcal glomer-
ulonephritis (AGN). Serum collected from
healthy children patients with impetigo, and
AGN will be tested by ELISA and RIA to deter-
mine the prevalence of this protein at different
ages, the presence of antibody, and the protec-
tive role of the antibody against AGN.

Investigators at Northwestern University and
the Streptococcal Disease Unit (San Fernando,
Trinidad) reported in the New England Journal of
Medicine on a 12-17-year followup on patients
with AGN in which only 3 of 760 patients dev-
eloped chronic renal disease.

U.S.S,R.

NIAID's formal involvement in the U.S.-
U.S.S.R. Agreement for Cooperation in the
Fields of Medical Science and Public Health has
been limited to influenza. This initiative, under

CDC coordination, provides for exchange of in-
formation, scientific meetings, visits by scien-
tists, and a mutual exchange of virus strains and
laboratory reagents. During FY 1982 the NIAID
initiated collaborative activities to identify new
hepatitis agents with the Institute for Polio-
myelitis.

United Kingdom

The Medical Research Council Clinical Re-
search Center (Harrow) collaborates with the
NIAID on the electron microscopy of bacteria
and on mycoplasma. The London School of
Tropical Medicine and Hygiene is collaborating
with the NIAID on the role of bacterial antigens
in immune response. The NIAID has initiated
collaboration with the Wellcome Research Lab-
oratories (Kent) on the developmental adapta-
tions of T. cruzi in vertebrate immune systems.
One extramural research grant to the Institute
of Animal Physiology deals with the genetics of
response to histocompatibility antigens. Four
English scientists hold NIAID-supported research
training grants in diverse areas.

Venezuela

Because 9 of the 10 priority areas in the bio-
medical and epidemiological research component
of the draft U.S.-Venezuelan Joint Health
Agreement are communicable diseases, the Di-
rector, NIAID, has agreed to serve as the interim
coordinator. In 3uly 1981 visits were made to the
Pan American Center for Research and Training
in Tropical Diseases (CEPIALET), the Venezu-
elan Institute of Scientific Investigation (IVIC),
the Tropical Medicine Institute (IMT), the Tor-
realba Institute, the National Institute of Health
(INH), and "La Trinidad" Medical Teaching Cen-
ter to determine the present level of scientific
exchange and opportunities for new and expand-
ed collaboration.

The Venezuelan Communicable Disease Coor-
dinator and Director of CEPIALET has since
visited the NIAID, and an NIAID scientist at-
tended a workshop entitled "Immunotherapy and
Pathogenesis of Leprosy" at CEPIALET. The
Venezuelan health coordinator and Director,
INH, visited the NIAID, and the Director of the
Torrealba Institute initiated discussions on col-
laborative research in Chagas' disease.

In August 1982 NIAID scientists spent several
weeks at CEPIALET to conduct immunologic
studies on Venezuelan patients with disseminated
cutaneous leishmaniasis and to evaluate the ef-
fect of heat therapy in inducing remissions.
CEPIALET has also initiated joint studies with
Tulane University on the effect of Albendazole
in the treatment of patients with onchocerciasis.
The NIH and CDC have initiated collaborative
work with the Ministry of Health and Zulia
health officials to characterize the delta agent

producing lethal hepatitis among isolated Amer-
indian populations. NIAID intramural scientists
continue joint investigations with researchers at
the University of Caracas in epidemiological,
clinical, and biochemical studies of human en-
terviral infection.

A Venezuelan delegation visited the NIH, the
FDA, Wistar Institute, and Wyeth Laboratories
to discuss collaboration on the development and
production of improved rabies vaccines.

Zambia

The NIAID continues long-standing scientific
exchange with the Tick Diseases Unit (Lusaka) in
the morphology and classification of African
specimens. In May 1981 the WHO Team Leader
of the Tropical Disease Research Center (Zam-
bia) visited the NIAID.

Zimbabwe

Following a visit from the Secretary of the
Ministry of Health in September 1980, the NIAID
has begun an exchange of scientific information
with the Blair Research Institute. An NIAID
Staff Fellow spent 3 months on the Infectious
Diseases Service of the University Hospital
(Salisbury).

Activities With International Agencies

NIAID intramural laboratories serve as WHO
Collaborating Centers in rickettsial diseases,
mycoplasma, and respiratory viruses other than
influenza. During FY 1979, WHO designated the
NIAID Microbiology and Infectious Diseases
Program as one of three collaborating centers on
interferon. The NIAID extramural program also
provides indirect support to U.S. institutions that
serve as WHO Collaborating Centers. Among the
most active are WHO Collaborating Centers in
arboviruses (Yale), enteroviruses (Baylor), in-
fluenza (CDC and St. Jude's Children's Research
Hospital), and immunology (Scripps Clinic). At
the invitation of WHO and TDR, NIAID staff and
awardees participated actively in meetings or
expert panels, as consultants to WHO or member
countries, or as faculty in WHO-sponsored
training activities. NIAID staff are particularly
active in support of the WHO Immunology Pro-
gram, which includes participation in the annual
WHO Immunology Course in Lausanne.

Extramural Programs

The NIAID extramural portfolio in tropical
medicine is drawn from nine areas of the Micro-
biology and Infectious Disease Program: the six
tropical diseases, ICIDR and TRU Programs,
general parasitology, tropical virology, tropical

bacteriology, tropical mycology, rickettsiae, and
vector pathogens.

Between 1960 and 1980 the NIAID supported
an ICMR Program, established under the author-
ity of P. L. 86-610. An ICMR was a research
organization sponsored by a U.S. health insti-
tution to provide a stable base for research and
training through overseas research centers. The
four ICMR units in Kuala Lumpur (Malaysia),
Dhaka (Bangladesh), Lahore (Pakistan), and Call
(Colombia) collectively served as a national re-
source to provide a pool of tropical disease in-
vestigators and to stimulate young scientists to
pursue careers in international biomedical
research.

The ICMR Program, however, has been super-
seded by four award mechanisms that provide
greater flexibility and cooperation between U.S.
tropical medicine specialists and their counter-
parts in developing countries. These mechanisms
are the International Collaboration in Infectious
Disease Research Program, the Tropical Disease
Research Units, the International Tropical Dis-
ease Research Fellowships, and the Senior In-
ternational Fellowships with an emphasis in
tropical diseases.

The ICIDR Program differs from the ICMR
Program in several ways. Perhaps the most im-
portant is the ICIDR emphasis on developing
peer relationships between U.S. institutions and
investigators and their counterparts. Its focus is
on infectious diseases, and at least 7Q percent of
the award must be spent overseas. The ICIDR
Program has two parts: the program project
(Part A) provides grants for collaborative re-
search in a series of related projects and the
exploratory project (Part B) divides grants be-
tween individual scientists in a single area. In
1982, Part A awards linked Harvard and Cornell
Universities with the Federal University of
Bahia, Brazil; the University of Illinois with
Chaing Mai University in Thailand; Michigan
State with Central Laboratories of the Sudanese
Ministry of Health; and the Tulane School of
Public Health with institutions in Colombia and
Haiti. Part B developmental grants linked Co-
lumbia University and the University of South
Florida with two Brazilian institutions; the Uni-
versity of Washington with the National Poly-
technic Institution in Mexico City; Ohio State
University with the University of Nigeria, Nsuk-
ka; and the University of Hawaii with the Uni-
versity of Aligarh in India.

For many years NIAID intramural laboratories,
particularly the Laboratory for Parasitic Dis-
eases and the Rocky Mountain facilities, have
been committed to basic research in tropical
diseases. With NIAID support, the Yale Arboviral
Research Unit also provides a university-based
center of excellence in tropical virology. The

NIAID-funded Tropical Disease Research Unit
Program is designed to expand this network to
outstanding U.S. institutions through awards for
multidisciplinary research in tropical medicine.
In addition to generating new knowledge, the
TRU Program provides the opportunity for in-
stitutional strengthening, research training for
young U.S. and foreign scientists, career devel-
opment, and a domestic counterbalance to the
ICIDR initiative overseas. In FY 1982, the TRU
award to the Peter Bent Bringham Hospital at
Harvard and to Case-Western University con-
tinued.

The ITDR Fellowship Program was initiated in
1979 with NIAID funds to provide a limited num-
ber of postdoctoral fellowships for scientists
from developing countries for advanced U.S.-
based research training in tropical disease. Ap-
plications were encouraged from developing
countries that may not be participating in the
FIC-supported International Research Fellowship
Program. The TDR Program has cooperated in
screening and identifying candidates for ITDR
fellowships. WHO also provides international
travel funds for successful candidates it has
nominated. In FY 1982 an Indian and a Peruvian
scientist completed the first two ITDR awards
for research training in leprosy and malaria,
respectively. Two new awards were made with
FY 1982 funds for a Chinese and an Egyptian
scientist to enter schistosomiasis research
training at the University of Pennsylvania.

The Senior International Fellowship, with an
emphasis in tropical diseases, provides 3-12
months of research support for mid-career and
senior U.S. scientists to conduct collaborative
tropical disease research projects outside the
United States. The initial three awards supported
research in Kenya, the Netherlands, and the
United Kingdom during FY 1981-82.

The Immunology, Allergic and Immunologic
Diseases Program is the other major NIAID
extramural awards program. Advances in immu-
nology have increased lAIDP international ac-
tivities with most industrialized countries. Rel-
atively recently, interest has grown in involving
the larger and/or more advanced developing
nations such as China, India, Thailand, and Ven-
ezuela in direct cooperation in immunology or in
application of new research tools to serious
endemic disease problems.

lAIDP now coordinates 18 domestic asthma
and allergic disease centers and four centers for
interdisciplinary research on immunologic dis-
eases. These constitute a network of U.S. in-
vestigators for research training and collabo-
ration. lAIDP also supports five lymphocyte
biology centers and in FY 1982 established the
first program project at Johns Hopkins Univer-
sity to study immune function in transplant

recipients. During FY 1982, the lAIDP Hybrido-
ma Cell Line Bank, established at the Anrierican
Type Culture Collection, continued to acquire
cell lines and began distribution to qualified
investigators.

Other lAIDP-supported activities include the
Allergen Research Reference Laboratory (Mayo
Clinic), the International Bone Marrow Trans-
plantation Registry (Mt. Sinai, Milwaukee), and
the Histocompatibility Seruna Bank. Countries
participating in these programs during FY 1982
included China, France, the Federal Republic of
Germany, 3apan, the Netherlands, Switzerland,
and the U.S.S.R.

Non-U.S. scientists may compete for NIAID
grant awards and apply directly for "sole-source"
contracts in any program area. Of the 23 awards
made in FY 1982 to investigators in 10 countries,
only 3 were relevant to tropical medicine. No
principal investigator came from a developing
country. The 23 foreign awards in FY 1982 rep-
resent a significant decline over the past 3
years: 27 awards were made in FY 1981 and ^6 in
FY 1980.

Although the major functions of the NIAID
Extramural Activities Program are program
analysis, project review, and grant or contract
management, its Research Resources Branch
also coordinates the Institute's continuing ef-
forts to provide reagents and resources to in-
vestigators and government agencies throughout
the world. During FY 1982 this activity amount-
ed to 11 major grants or contracts for the dis-
tribution of microorganisms, parasites, or ani-
mals for research relevant to tropical medicine;
in this area, 7 fewer awards were made than in
FY 1981. Also, reduced costs resulted from
phase-outs, transfers of functions outside the
NIAID, consolidations, and the less frequent
provision of reference materials from intramural
laboratories.

In addition to these activities in tropical med-
icine, this branch continues to provide research
and reference reagents not available through
commercial sources for enteroviruses, adeno-
viruses, rhinoviruses, myxoviruses, the agents
and antigens of hepatitis A and B, coronaviruses,
herpesviruses, interferons, mycoplasmas, and
reoviruses. During FY 1982, arrangements were
made with the Plum Island Animal Disease Cen-
ter to process the immune ascitic fluids of Af-
rican swine fever. Rift Valley fever, African
horse sickness, and bovine ephemeral fever.
Complement Compound C3 and penicillin
products are provided in association with the
American Type Culture Collection. Hypersen-
sitivity pneumonitis antigens and antisera are
being made available in cooperation with the
Mayo Clinic. Additional allergenic products
made available include ragweed and rye grass

antigens and venoms from honey bees, hornets,
yellow jackets, and other hymenoptera.

Intramural Programs and Activities

The NIAID intramural program now has 13
research laboratories or branches, three of which
are located at the Rocky Mountain facilities in
Hamilton, Montana. Although all of these lab-
oratories have significant international health
activities, the major portion of tropical medicine
research is concentrated in the Laboratory of
Parasitic Diseases. The Epidemiology Branch of
the Rocky Mountain Laboratory also sets aside a
substantial portion of its resources for medical
zoology and vector studies.

At Bethesda, the Laboratory of Infectious
Diseases increasingly emphasizes collaborative
investigations into respiratory viruses, diarrheal
diseases, and hepatitis.

Recent advances in immunology and labora-
tory techniques are now being applied to diseases
prevalent in the tropics with a consequent
tendency for broader involvement by basic bio-
medical research laboratories in international
research. The Laboratory of Microbial Immunol-
ogy, for example, is active in studying the im-
mune reaction to several parasitic infections
such as trypanosomes, malaria, and amebae in
experimental models. The Laboratory of Clinical
Investigation and the facilities at the Clinical
Center are available for detailed studies on U.S.
or foreign patients with known or suspected
tropical diseases.

While the actual level of intramural research
in tropical medicine increased by only 7 percent
between 1981 and 1982, this support is enhanced
considerably through NIAID intramural inves-
tigators' collaboration with colleagues outside
the United States. This joint research extends to
many areas beyond the scope of tropical medi-
cine in the exchange of scientists, data, diag-
nostic material, or the introduction and stand-
ardization of laboratory techniques. Collabora-
tion immediately relevant to Tropical Medicine
also occurs within the NIH and with other Fed-
eral agencies, particularly the Centers for Dis-
ease Control, the Office of Naval Research, the
Walter Reed Army Institute of Research, and the
Bureau of Biologies. Intramural scientists are
also involved in the technical work of bilateral
(USAID), multilateral (WHO, PAHO), or private
(Rockefeller Foundation, National Academy of
Sciences) agencies concerned with tropical med-
icine and internationeil research.

In FY 1982, 30 intramural projects included
significant collaboration with scientific insti-
tutions in 27 foreign countries. The most fre-
quent collaborators were from France and

Switzerland, followed by India and the United
Kingdom. Australia, Canada, Egypt, the Federal
Republic of Germany, Ghana, and Japan each
had two cooperating units. One unit also existed
in Belgium, Brazil, the Dominican Republic, the
German Democratic Republic, Israel, Italy,
Panama, Puerto Rico, Sweden, and the U.S.S.R.

ada, Colombia, Denmark, Hungary, Lebanon,
Mexico, the Netherlands, the Philippines, Sierra
Leone, South Africa, the U.S.S.R., and Yugo-
slavia.

International Conferences, Seminars,
and Meetings

Visiting Program

The NIAID intramural program benefits con-
siderably from the participation of foreign vis-
iting scientists. In FY 1982, for example, the
NIAID provided funds for 71 long-term visiting
scientists and 5 experts from 26 countries. The
NIAID provided laboratory space and reagents
for 33 guest scientists whose salaries were paid
by their home institution, government, or source
other than the NIH. The largest number were
from Japan (19), the United Kingdom (10), India
(9), China (8), and Australia (7). Smaller numbers
represented France (6), Brazil (5), Argentina (4),
and Taiwan (4). There were three scientists from
Germany (Federal Republic), Nigeria, and Swe-
den; two from Israel, Italy, Korea, Switzerland,
and Venezuela; and one from Bangladesh, Can-

During FY 1982 the NIAID organized, funded,
and actively participated in a variety of scien-
tific meetings relevant to tropical medicine and
international research. Almost a dozen meetings
were major national and international meetings,
conferences, and congresses concerning research
issues such as interferon, sexually transmitted
diseases, measles immunization, diarrheal dis-
eases, and infectious and parasitic diseases. An
additional l'^ meetings related to bilateral re-
search programs, 10 of which were associated
with various activities of boards working under
the U.S.- Japan Cooperative Health Program or
programs in Latin America, the Caribbean, and
the Middle East. Also, a number of conferences,
seminars, and meetings were held in connection
with support of research under the auspices of
such organizations as WHO, PAHO, and USAID.

Chapter X
National Institute of Child HeaUh and Human Development

Introduction

The mission of the National Institute of Child
Health and Human Development (NICHD) is to
conduct and support research on the reproduc-
tive, developmental, and behavioral processes
that determine the health of children, adults,
families, and populations.

The Institute's programs stem from the as-
sumption that adult health and well-being are
determined in part by episodes in early life, that
human development is a continuous process
throughout life, and that reproductive processes
and the management of population problems are
of major concern, not only to the individual but
also to the whole of society.

The NICHD supports research in the repro-
ductive sciences that enables men and women to
regulate their fertility with methods that are
safe, effective, and acceptable to various popu-
lation groups and to overcome problems of in-
fertility. In the social and behavioral sciences,
Institute-sponsored research is aimed at under-
standing the causes and consequences of popu-
lation change. Research for mothers, children,
and families is designed to advance knowledge of
fetal development, pregnancy, and birth; to
identify the prerequisites of optimal growth
through infancy, childhood, and adolescence; and
to contribute to the prevention and treatment of
mental retardation.

The pursuit of new knowledge is basic to the
Institute's mission. The NICHD regards inter-
national cooperation as a catalyst for the devel-
opment of that new knowledge. Through a vari-
ety of mechanisms, the Institute has maintained
and expanded its activities in the international
exchange of scientific information. Activities
are conducted under bilateral agreements and
the Special Foreign Currency (P.L. ^^80) Program
and in cooperation with international agencies
and the NIH Visiting Program.

In addition, the NICHD directly supports for-
eign investigators through research grant and
contract awards to their home institutions and
indirectly through awards to U.S. institutions
with foreign components or involvement in for-
eign research.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

China

In January 1979, the United States and China
signed an Agreement for Cooperation in Science
and Technology. The agreement, containing
specific allowances for cooperative activities in
a number of scientific fields, was furthered in
June 1979 when health officials from both
countries signed the Protocol for Cooperation in
the Science and Technology of Medicine and
Public Health. Areas of cooperation between the
NICHD and counterparts in China include human
genetics, public health and health services re-
search, child development and nutrition, and
reproductive physiology and family planning.

As a followup to the 1981 visit to China by
NICHD staff participating in the U.S. Delegation
on Reproductive Physiology and Family Planning
Techniques, a plan for a study on pregnancy
outcomes has been designed for implementation
in Shanghai County. The Institute has forwarded
the study—which includes perinatal mortality,
low birth weight, and congenital malforma-
tions—through channels to the Chinese
Coordinator.

India

In accordance with the Indo-U.S. Bilateral
Agreement dating from 197^, and in cooperation
with the U.S. -India Subcommission on Science
and Technology and the India Council for Medi-
cal Research, the NICHD staff has participated
in meetings to advance collaborative research in
the population sciences and in nutrition. A Work-
ing Group on Reproduction and Contraceptive
Research oversees the development of the coop-
erative program.

Japan

The NICHD participates in the efforts of the
U.S. Malnutrition Panel Program of the U.S.-
3apan Cooperative Medical Sciences Program by
supporting research studies intended to develop
solutions to the nutritional problems of special
concern to Asian people.

Nigeria

In September 1981, Nigeria and the United
States signed a formal agreement to establish
cooperative health activities. The plan specifies
U.S. -Nigeria research collaboration in nutrition,
beginning with workshops to develop preliminary
research protocols, followed by workshops in the
United States that will include Nigerian inves-
tigators.

Poland

Under the U.S.-Poland Collaborative Research
Agreement, a study of the epidemiology of
neural tube defects continues at the Krakow
Institute of Pediatrics.

Yugoslavia

A collaborative study of breast cancer as a
possible result of oral contraceptives is in prog-
ress with the Institute of Oncology in Ljubljana,
under the U.S. -Yugoslavia Joint Board for Sci-
entific and Technological Cooperation.

Activities With International Agencies

World Health Organization

NICHD staff serve as consultants to the WHO
Special Program of Research, Development and
Research Training in Human Reproduction and as
members of the WHO Committee on Resources
for Research about Human Reproduction.

Collaborative and cooperative efforts with
WHO on the development of safe and effective
methods of fertility regulation for both men and
women have been extensive. These activities
range from mutual consultation to joint product
development.

European Medical Research Council

Staff of the NICHD are members of the council's
Advisory Subgroup on Reproduction, which was
established to identify areas of cooperation
within Europe and between Europe and the
United States on research in reproduction. The

subgroup also interacts with the pharmaceutical
industry to obtain information about the indus-
try's research projects with a possible a bearing
on human reproduction.

Extramural Programs

Components of the NICHD extramural re-
search program are the Center for Population
Research, the Center for Research for Mothers
and Children, and the Epidemiology and Biome-
try Research Program.

The Center for Population Research is respon-
sible for the primary Federal research effort in
the population sciences. Included are studies on
human fertility and infertility, the development
and evaluation of methods of fertility regulation,
and the social and behavioral aspects of these
problems in relation to individuals and to popu-
lations. Through research grants and contracts,
the NICHD supports investigators around the
world.

A research project supported by the Center
for Population Research is studying the motiva-
tions and adjustments of migrants from a rural
region in the Philippines who resettled either in
Manila, the major urban area of the country, or
in Honolulu, a key U.S. destination city. The
study has provided new insights into the reasons
for moving, the choice of destinations, and the
effect of migration policies on internal and
international migration flows.

Migration decisions, the study shows, are
based on a complex set of familial and quality-
of-life consideration, and are not dictated simply
by economic circumstances. The study found
that household and family strategies in- fluence
decisions about moving to a greater extent that
individual desires do. Out-migrants often
maintain substantial obligations and con- tinuing
contacts with their previous households through
monetary remittances, visits, and cor-
respondence. The study also confirmed the im-
portance to decisionmaking of assistance from
relatives and friends located in different poten-
tial destinations.

The Center for Research for Mothers and
Children supports biomedical and behavioral
research aimed at making possible pregnancies
and births that produce sound infants, who can
grow to adulthood free of disease and disability.
Since its inception, the NICHD has promoted
research on the role of nutrition in the preven-
tion of disease and disability as part of the
strategy for achieving that goal.

A nutritional anthropologist is currently
studying the relationship between culturally
induced malnutrition in young children and pro-
tection against malaria in the Sudest Island of

New Guinea. Malaria, endemic in this area of
New Guinea, represents a major cause of child-
hood mortality. Feeding animal protein to
children under age three is traditionally pro-
scribed. The resulting malnutrition produced by
this prohibition may offer protection against the
malaria Plasmodium, which appears to be more
sensitive to undernutrition than the human host.
The current working hypothesis is that tradi-
tional food taboos among these islanders rep-
resent a cultural adaptation to the local envi-
ronment.

This observation in the field has implications
for developing more sophisticated single nutrient
deficiencies in the human host to protect against
disease. For instance, iron depletion by lacto-
ferrin in the gastrointestinal tract of human
newborns may reduce or alter the resident bac-
terial colonies there.

The Center for Research for Mothers and
Children also supports studies on the human
learning process and communicative disorders. A
researcher in England is measuring the impact of
otitis media with effusion (middle ear infection,
OME) on the educational/communications com-
petence of English-speaking children. The study
will determine if persistent OME is associated
with educational and/or linguistic retardation,
what types of problems may result, and if ways
can be found to provide early detection of such
problems.

The Epidemiology and Biometry Program is
collaborating with the Department of Epidemi-
ology at Ben Gurion University, Beer Sheva,
Israel, in a study of the effects of westernization
on infant feeding practices among Bedouin pop-
ulations undergoing transition from a nomadic to
a more settled lifestyle. Data are being col-
lected to test the hypothesis that, as this trans-
ition takes place, less exclusive breast feeding
and more bottle feeding and mixed breast and
bottle feeding will be practiced. This study
examines the effects of infant feeding, use of
hecilth services, and other aspects of a changing
lifestyle on the rate of growth and morbidity
during the first year of life.

Collaboration is continuing with the University
of Trondheim in Norway to study the outcome of
successive pregnancies. The routine linkage of
vital record systems in Norway with death rec-
ord systems, available now for over a decade,
provides unusual opportunities for epidemiolog-
ical investigation of birth outcome. Similar
linkage has occurred more recently in Sweden,
and the Epidemiology and Research Program has
developed collaborative contacts with the Uni-
versity of Uppsala in exploring these data
systems.

International Conferences, Seminars, and Meetings

Collaborative endeavors with WHO in the area
of fertility regulation continued in 1982 with a
"Consultation on the Chemical Synthesis of
Fertility Regulating Agents" held at the NIH and
cosponsored by WHO and the NICHD.

NICHD staff attended the European Medical
Research Council symposium in Paris entitled
"Epidemiological Aspects of Human Reproduc-
tion," which included a session on fertility and
sterility.

Intramural Programs and Activities

NICHD intramural scientists engage in in-
ternational collaboration in research projects
relevant to their own research interests at the
NIH. Often these collaborations are formal,
structured, and endure for many years. For
example, one NICHD laboratory chief serves as
genetic coordinator with China under the U.S.-
China Health Protocol.

Research opportunities within the Intramural
Program of the NICHD include clinical studies in
the areas of human genetics, endocrinology, and
reproductive physiology, as well as develop-
mental psychology.

NIH Visiting Program and Health Scientist
Exchange Programs

The NIH Visiting Program provides opportun-
ities for recent postdoctoral fellows and senior
scientists from abroad to conduct collaborative
research in the United States. More than 50
internationals from a dozen countries were in-
volved in the NICHD Intramural Research Pro-
gram during 1982. The usual length of the visit is
2 to 3 years. In addition to participants in the
formal Visiting Program, there are a large num-
ber of foreign visitors who come as guest work-
ers, whose financial support comes from sources
other then the NICHD.

The activities of all these scientists are pur-
sued in 11 basic science laboratories or clinical
research branches of the NICHD, including the
Developmental Pharmacology Branch, the Endo-
crinology Branch, the Laboratory of Develop-
mental Neurobiology, the Laboratory of Neuro-
chemistry and Neuroimmunology, the Laboratory
of Theoretical Biology, the Human Genetics
Branch, and the Laboratory of Developmental
and Molecular Immunity.

Chapter XI
National Institute of Dental Research

5!»i

Introduction

In the search for a better understanding of
oral health and disease—problems that recognize
no barriers of geography— the promotion of den-
tal research internationally cannot be separated
from the promotion of dental research domesti-
cally. The National Institute of Dental Research
(NIDR) encourages the programing of grants,
contracts, and intramural research wherever the
best data sources and expertise lie. The Institute
emphasizes staff participation in and support of
international meetings and the publication of
proceedings, the funding of foreign grants and
contracts, and the provision of research oppor-
tunities for visiting scientists.

In its mission to support and facilitate re-
search on the etiology, diagnosis, prevention, and
treatment of oral diseases and malfunctions, the
Institute's six major program areas serve as the
central force for programing: dental caries;
periodontal diseases; craniofacial anomalies; soft
tissue, stomatology, and nutrition; restorative
materials; and pain-control/behavioral studies.
The Intramural Research Program, organized
according to basic biomedical disciplinary lines,
and the National Caries Program invite visiting
scientists to augment basic scientific investi-
gations, primarily, and, to a limited extent,
clinical research projects.

During FY 1982, the Institute funded nine
foreign grants in the research areas of dental
caries, tooth mineralization, pain control, cra-
niofacial anomalies, and composition of connec-
tive tissue. In Bethesda, the Institute's intra-
mural program supported or sponsored 33 Visit-
ing Fellows, 7 Visiting Associates, and 7 Visiting
Scientists. They came from 17 countries, 8 in
Europe, 6 in Asia, 2 in Latin America, and 1 in
the Near East.

The Institute encourages a wide exchange of
scientific information. NIDR Abstracts informs
dental investigators of current developments in
special areas of interest. This publication is
distributed to about 150 foreign colleagues.
Dental scientists around the world have been
asked to register their research projects with the
Dental Research Data Officer of the NIDR for
inclusion in an annual publication. Dental Re -
search in the United States and Other Countries.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

Under the auspices of the U.S.-Nigeria Coop-
erative Health Agreement, the NIDR assisted
the Nigerian Ministries of Health and Science
and Technology, as well the WHO, the Federa-
tion Dentaire Internationale, and the Interna-
tional Association for Dental Research, in plan-
ning and conducting the Conference on Dental
Research Needs and Opportunities in the WHO-
Region of Africa. The conference was held in
February 1982 in Lagos, Nigeria, and brought
together more than 20 countries whose repre-
sentatives agreed that a WHO International
Collaborative Center for Dental Research and
Oral Health would be an appropriate means to
stimulate and nurture research in this region of
the world. The Nigerian Government expressed a
wish to host such a center. The protocol for the
center is currently being circulated in the region
to solicit financial support.

Activities With International Agencies

The Special Assistant to the Director, NIDR,
served as a consultant to the USPHS/WHO In-
ternational Collaborative Study of Dental Man-
power Systems in Relation to Oral Health Status.
In that capacity she was a technical advisor to
the WHO Regional Office for Europe to explore
the implications of the collaborative study for
the delivery of dental services in northern and
western Europe.

Extramural Programs

International collaboration during the year
continued or was initiated between NIDR sci-
entists and researchers at the following insti-
tutions by means of grant support:

• University of New South Wales and the
Institute of Dental Research, Sydney, Aus-
tralia (surface structure of oral bacteria);

• University of Queensland, Brisbane, Aus-
tralia (surface composition of apatites);

• McGill University, Montreal, Canada (pro-
collagens in dental tissues);

• University of Toronto, Canada (brain stem
mechanisms and dental pain associated with
trigeminal nucleus caudalis);

• College de France, Paris (migration and
differentiation of neural crest cells);

• Gothenburg University, Sweden (plaque
control and healing after periodontal sur-
gery); and

• Hebrew University of Jerusalem, Israel
(mineralization of tooth enamel).

International Conferences, Seminars,
and Meetings

In 1982, 29 NIDR scientists attended and con-
tributed to 57 meetings in 21 foreign countries
and 5 continents. Of these meetings, 19 were
seminars and discussions of collaborative re-
search. The other occasions were workshops,
symposia, and conferences such as the Tenth Sao
Paulo Congress of Odontology and Latin Ameri-
can Seminar of Odontology-Sao Paulo, Brazil;
the Twelfth European Leucocyte Culture Con-
ference-Vienna, Austria; the First Erik Fern-
strom Symposium (neurology)-Lund, Sweden; a
Ciba Foundation Symposium (protein chemis-
try)-London, England; the Third Merieux Con-
ference on the Pathology of Viral Diseases-Lyon,
France; the Conference on Genetics of Industrial
Microorganisms-Kyoto, Japan; and the Interna-
tional Sociological Association Symposium on
International Collaborative Research in Health-
Mexico City, Mexico. The NIDR also provided
support to enable foreign scientists to give
papers at four conferences in the United States.

NIDR staff of the National Caries Program
planned and hosted the first U.S. meeting of the
European Organization for Caries Research, in
Annapolis, Maryland, in June 1982 in honor of
the tenth anniversary of the establishment of the
National Caries Program. The Special Assistant
to the Director chaired the International Rela-
tions Committee of the International Association
for Dental Research and participated actively in
promoting dental research capacity in developing
countries. She also assisted the Division of
Health Policy Research and Education at Har-
vard University through a cooperative assign-
ment to develop initiatives on international
aspects of health and human behavior in devel-
oping countries, and on issues of health science
policies related to the allocation of resources for

research in industrialized societies. She prepared
agenda items on issues of international health
policy relevant for pursuit by the NIH and/or
academic institutions.

Intramural Programs and Activities

The microbial systematics section of the In-
stitute continues to collaborate with the Ameri-
can Type Culture Collection, the Centers for
Disease Control, the FDA, the VA, and numerous
researchers in foreign counterpart organizations
in regard to the worldwide data bank for infor-
mation on the diverse strains of human oral
microbiota.

The system devised for bacteria has now been
expanded to include other organisms such as
yeasts, molds, algae, protozoa, and hybridomas
so that confusing relations among these life
forms can be systematized and certain contro-
versial epidemiological data can be clarified.
Also, to help identify unknown bacteria isolated
from the mouth, computer-aided patterns or
matrices have been constructed and are avail-
able to researchers throughout the world.

An NIDR scientist is collaborating with an
Israeli investigator, at the Weizmann Institute,
who is crystalizing osteonectin—an important
protein in bone matrix—in order that the pro-
tein's structure may be analyzed by X-ray dif-
fraction. Understanding the three-dimensional
structure of osteonectin will allow scientists to
determine how the protein accomplishes its
biological activities.

Scientists in the NIDR Laboratory of Bio-
chemistry, collaborating with investigators at
the University of Monash, Melbourne, Australia,
are using the long-lasting techniques of organ
culture devised by the Australians. They are
studying how cartilage cells synthesize and break
down, over periods of several weeks, the large
proteoglycan molecules that act as shock ab-
sorbers to cushion loads on human joints.

NIH Visiting Program and Health Scientist
Exchange Programs

A Visiting Fellow from Korea is collaborating
with staff of the Laboratory of Microbiology and
Immunology, NIDR, in obtaining circular DNA
from bacteria. Genes in this DNA control the
ability of bacteria to digest sugars. The genes
have been cloned into other bacteria so that the
molecular basis of this genetic process can be
studied and so that eventually tooth decay can
be controlled more effectively.

In the same laboratory, a scientist from the
New Zealand Dairy Research Institute, Palmer-

ston North, has shown that a sugar variant
(2-deoxyglucose) interferes with the ability of
various bacteria to absorb sugars and makes it
hard for them to grow. This research is poten-
tially useful for developing sugar analogues that
might be added to the diet to reduce tooth decay.
From herpesvirus type 1, the cause of fever

blisters, an English expert has isolated a gene
that codes for a specific protein and has used
recombinant DNA techniques to introduce this
gene into a common bacterium so that the bac-
terium will produce the protein in quantity.
These preliminary steps may result in the pro-
duction of a safe vaccine against this disease.

Chapter XH
National Institute of Environmental Health Sciences

Introduction

During recent decades, sonne of the more
urgent health problems confronting the general
population have arisen from human exposure to
chemical and other physical factors in the en-
vironment. Health risks emanating from man's
environment are not a new phenomenon. How-
ever, with the post-World War II growth in in-
dustry and commerce and the acceleration of
industricdization in developing countries, recog-
nition and concern for the potentially adverse
effects of environmental agents on human health
and the ecosystem have become worldwide.
Public and private organizations throughout the
world have tried to anticipate and avoid these
problems through support of environmental
health research. The National Institute of Envi-
ronmental Health Sciences (NIEHS) serves as the
principal U.S. Federal agency for biomedical
research on the effects of chemical, physical,
and biological environmental agents on human
health. The research aims of the NIEHS focus on
identifying and investigating environmental
factors that may have deleterious effects on
human health (e.g., mutations, cancer, lung
disease, birth defects), on quantifying these
effects, on understanding the mechanisms of the
action of toxic agents on biological systems, and
on developing methods for testing and predicting
the toxicity of chemicals. Through these efforts,
NIEHS research provides the basic information
necessary for establishing disease prevention
programs. These goals transcend national bound-
aries, and the NIEHS plays a leading role in the
organization and development of international
efforts to meet environmental health problems.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

China

Cooperation between the United States and
China in environmental health was initiated
during 1980 under the U.S.-P.R.C. Agreement
for Cooperation in the Science and Technology

of Medicine and Public Health. The NIEHS par-
ticipates in public health and health services
research, which includes both environmental and
occupational health concerns. Exploratory dis-
cussions with scientists from both countries have
been held during exchange visits with initial
discussions centering around cooperation in the
following areas: biochemical and epidemiological
research related to asbestosis and silicosis; bio-
chemical and epidemiological research related to
heavy metals; development and validation of
short-term test methods to detect and assess
carcinogens, mutagens, and teratogens in the
environment; and the application of standard
toxicological test methods and the extrapolation
of laboratory animal data to man. During FY
1982, an intramural scientist presented a series
of lectures on biochemical toxicology at the
Chinese Academy of Medical Sciences in Beijing
and visited Shanghai to discuss plans for future
cooperation with scientists from the First Medi-
cal College of Shanghai, Fudan University, and
the Shanghai Cancer Institute.

Egypt

Cooperation between American and Egyptian
environmental health scientists is being carried
out under the auspices of the U.S.-Egypt Joint
Working Group on Health Cooperation. The
NIEHS has been assigned responsibility for the
U.S. Subcommittee on Environmental and Occu-
pational Health of the 3WGHC. Efforts to date
have consisted of a workshop held in Egypt in
early 1980 to identify the biomedical impacts of
technology transfer. During 1982, a series of
training workshops involving 2'f U.S. scientists
and over 100 Egyptian scientists was held In
Egypt focusing on the following areas: pesti-
cides, trace metals, radiation, environmental
management, and mutagenesis. An information
unit for environmental impact assessment is also
being established. This project is directed to the
needs expressed by the Egyptians for information
on environmental and occupational health. These
activities are funded largely through the NIH
Special Foreign Currency (P.L.-'tSO) Program.

Italy

Cooperation between American and Italian
environmental health scientists is being carried

out under the joint U.S. -Italy Memorandum of
Understanding signed by the Secretary, DHEW,
and the Italian Minister of Health in 1977. Since
that time, there have been several exchange
visits between scientists of both sides and dis-
cussions aimed at defining areas of cooperation.
Under discussion are possible collaborative ac-
tivities concerned with mutagenicity testing,
testing of complex mixtures, long-term bioassay
testing, and quantitative risk assessment.

In addition to these activities, NIEHS staff
have been involved in meetings and consultations
concerned with the explosion of a chemical
reactor in Seveso, Italy, which resulted in expo-
sure of a large population to dioxins.

Japan

Cooperation between American and Japanese
scientists on environmental health problems
takes place under two formal agreements: the
U.S.-3apan Cooperative Medical Sciences Pro-
gram and the Agreement on U.S.-3apan Cooper-
ation in Research and Development in Science
and Technology. Under the U.S.-3apan Coopera-
tive Medical Sciences Program, American envi-
ronmental health scientists participate in the
Panel on Environmental Mutagenesis and Car-
cinogenesis chaired by the Associate Director
for Genetics, NIEHS. 3oint areas of research
focus on the detection of mutagenic and car-
cinogenic chemicals using both in vitro and in
vivo test systems and on monitoring human pop-
ulations for evidence of exposure to mutagenic
and carcinogenic chemicals; joint studies on
carcinogens and mutagens in the diet and dietary
tract have been particularly productive. To
further mutual understanding of these issues, a
U.S.-3apan Workshop on Genetic Toxicology and
Food Mutagens was held in the United States
during FY 1982.

Under the U.S.-3apan Agreement on Coopera-
tion in Research and Development in Science and
Technology, the NIEHS participates in the tox-
icology program area in the counterpart working
group on health. Exploratory discussions on
cooperation in this program were initiated in
1980 and 1981 by an exchange of scientists so
that they could become familiar with the or-
ganizations and research programs in this area.
In the toxicology program area, discussions cen-
tered on cooperation in the following subjects:
development and validation of short-term test
methods to detect carcinogens and mutagens;
development of methods to test volatile chemi-
cals; development of methods to study mixtures
of chemicals; studies on the chemical initiation
and promotion of cancer; and the development of
approaches to quantitative risk assessment.
During FY 1982, the Special Assistant to the
Director for International Affairs and the
Assistant to the Deputy Director, Toxicology
Research and Testing Program, visited 3apan to

explore further areas of cooperation and for-
malize the exchange of quantitative data from
3apanese and U.S. mutagenicity testing pro-
grams. In accordance with the Memorandum of
Understanding with the U.S. Department of
Labor, NIEHS scientists also held extensive
discussions with the 3apanese Ministry of Labor
staff regarding scientific procedures relating to
bioassay protocols and regarding arrangements
for an exchange of information on chemicals
tested and test results.

U.S.S.R.

Collaboration between Soviet and American
environmental health scientists is carried out
under the auspices of two cooperative agree-
ments between the United States and the
U.S.S.R.

Under the U.S.-U.S.S.R. Medical Science and
Public Health Cooperative Agreement, the
NIEHS is the lead U.S. agency for environmental
health. Formal collaboration in environmental
health research between the United States and
the U.S.S.R. is in its tenth year. An exchange of
information and workshops have been held on the
following topics: developmental toxicology;
biological effects of metals; behavioral toxicol-
ogy; and biological effects of physical factors in
the environment. The proceedings of these work-
shops were published in both countries, and over
50 scientific papers have been published by
American and Soviet scientists on the results of
environmental health research conducted under
this agreement. In addition, a Russian-English
Glossary of Environmental Health Terminology
was published in both countries to assist com-
munications between scientists.

A workshop was held in the United States in
May 1982, entitled "Nervous System Effects of
Electromagnetic Waves (0-300 GHz)." Ten U.S.
scientists and eight Soviet scientists participated
in the workshop held at the NIEHS. The purpose
of the workshop was to discuss existing methods
of evaluating the impact of electromagnetic
waves in the environment on the central nervous
system and behavior to select those methods
that appear to be most sensitive. As a result of
the workshop, a duplicate project was developed
to test and standardize the methodological ap-
proaches to be used for evaluating effects on the
central nervous system. A scientist from the
NIEHS and one from the Bureau of Radiological
Health, FDA, visited the Soviet Union in Sep-
tember 1982 to discuss specific details and reach
an agreement on the exact procedures for ex-
posing the animals and for measuring the above
parameters.

The NIEHS also participates in the U.S.-
U.S.S.R. Agreement on Cooperation in the Field
of Environmental Protection, which is admini-
stered for the United States by the Environ-
mental Protection Agency. The Director, NIEHS,

serves as the DHHS representative to the Envi-
ronmental Protection Agreement and cochair-
man of the working group concerned with the
biological and genetic effects of pollution.

Activities With International Agencies

NIEHS staff have been active participants in
WHO programs for a number of years. In 1975,
WHO designated the NIEHS as a Collaborating
Center for Environmental Health Effects. During
FY 1982, the Institute, under the leadership of
the Associate Director for Health Hazard
Assessment, continued to provide advice and
scientific expertise to WHO headquarters and
WHO regional offices.

In 1979, WHO established the International
Program on Chemical Safety (IPCS), a coopera-
tive undertaking involving WHO, the United
Nations Environmental Program, the Interna-
tional Labor Organization, and their respective
member states. Since the signing of a coopera-
tive agreement between the NIEHS and WHO in
1980, the NIEHS has assumed the function of.
lead institution within the IPCS for such activ-
ities as international evaluations of biological
effects of chemicals and health hazard assess-
ments, and review and/or validation of methods
for testing of mutagenicity, carcinogenicity,
neurobehavioral toxicity, and toxicity to repro-
ductive function. Assisting NIEHS participation
in the IPCS is a WHO Interregional Research
Unit, established at the NIEHS in 1981.

The objectives of the IPCS are (1) to encour-
age international cooperation in the evaluations
of the effects of chemicals on human health and
on the quality of the environment; (2) to coor-
dinate chemical testing and toxicological re-
search to eliminate unnecessary duplication of
effort; (3) to develop international protocols for
laboratory testing, epidemiological studies, and
risk assessment; {^) to develop international
guidelines and exposure limits for chemicals in
air, water, and food; and limits for hazardous
chemicals in workplaces; (5) to develop response
mechanisms for coping with chemical emergen-
cies that may be international in scope; and (6)
to promote training and development of man-
power in areas and specialties necessary for the
achievement of program goals.

The Director, NIEHS, and the Special Assist-
ant to the Director for International Affairs,
NIEHS, attended the third Program Advisory
Committee of the IPCS, held in June 1982 in the
U.S.S.R. The PAC is responsible for evaluating
the workplans and progress of the IPCS and for
providing guidance on the administrative and
scientific aspects of the IPCS objectives.

The Associate Director for Genetics chaired
two working groups held in Geneva during 1982
to further develop the "IPCS Collaborative Study
on Short-Term Tests for Genotoxicity and Car-

cinogenicity." The purposes of the program are,
on an international scale, to: (1) evaluate in vitro
short-term tests for mutagenesis and carcino-
genesis, (2) evaluate short-term in vivo assays
for mutagenicity, and (3) develop standardized
protocols for the performance of short-term
tests for mutagenicity. The choice of chemicals
and of participating investigators in these stud-
ies has been finalized, and provisions for dis-
tributing these compounds have been made. A
mutagenesis expert from the NIEHS Cellular and
Genetic Toxicology Branch also participated in
these meetings.

In FY 1982, the chief of the Laboratory of
Reproductive and Developmental Toxicology
(LRDT) and the Head, Experimental Teratogen-
esis Section, LRDT, participated in an IPCS/
WHO-sponsored workshop, "Methods for the
Integrated Evaluation of Risks for Progeny As-
sociated with Prenatal Exposure to Chemicals,"
held in Prague, Czechoslovakia. This workshop
was part of an ongoing effort to help organize
and participate in an international effort to
identify improved laboratory and clinical ap-
proaches for detecting birth defects.

Also within the framework of IPCS, the NIEHS
Office of Health Hazard Assessment (OHHA), in
collaboration with the WHO Interregional Re-
search Unit, prepared draft evaluation docu-
ments on 2,6-toluene diamine and phthalic acid
esters. These drafts have been transmitted for
review and revision to a number of national focal
points for the IPCS. The OHHA is also respon-
sible for the scientific editing and updating of
the second volume of a WHO monograph "Prin-
ciples and Methods for Evaluating the Toxicity
of Chemicals."

NIEHS staff also took part in a workshop en-
titled "Methods for Estimating Exposure, Quan-
tifying Risk to Human Health, and Predicting
Chemical Injury to Ecosystems," organized by
the Scientific Group on Methodologies for the
Safety Evaluation of Chemicals in July 1982 in
Rome, Italy. This group is one of the IPCS
projects operated jointly with the Scientific
Committee on Problems of the Environment of
the International Council of Scientific Unions
and the United Nations Environment Program.
The objective of the group is to examine meth-
ods for the predictive evaluation of the adverse
effects of chemicals on human subjects and
other forms of life. This was the third such
workshop.

In other WHO activities, the Chief of the
Laboratory of Reproductive and Developmental
Toxicology, NIEHS, continued as temporary
adviser to the Toxicology Review Panel of the
WHO Special Program of Research, Develop-
ment, and Research Training in Human Repro-
duction. The review panel meets twice a year to
consider the potential toxicity associated with
current and future approaches to contraception.
The Chief of the Laboratory of Reproductive and

Developmental Toxicology has also been invited
by the Office of Occupational Health, WHO, to
join an international group studying occupational
hazards to reproductive functions.

Extramural Programs

Through its extramural program, the NIEHS
provided grant support to (1) the State Univer-
sity of Leiden, Leiden, the Netherlands, to study
the induction of genetic damage by chemical
mutagens; (2) the University of Western Ontario,
London, Canada, to study the nature of lead-
binding and mercury-binding nuclear proteins;
and (3) the University of Turku, Turku, Finland,
to study gastrointestinal and pulmonary meta-
bolic functions. In addition, the Extramural
Program provided funds to the WHO Interna-
tional Program on Chemical Safety in support of
that cooperative effort.

International Conferences, Seminars,
and Meetings

To provide an opportunity for scientists from
different countries to exchange research results
and stimulate scientific collaboration, the NIEHS
continues to support a number of conferences
and seminars involving international participa-
tion. Examples of the types of seminars and
conferences supported in part by the NIEHS this
past year include:

• Joint American-Swedish Workshop on
Individual Susceptibility to Genotoxic
Agents in the Human Population

• Workshop on the Utilization of Mammal-
ian-Specific Locus Studies in Hazard
Evaluation and Estimation of Genetic
Risk

• Symposium on Psoralens

• Seminar on the Role of DNA Lesions and
Promotion in Organ-Specific Tumors

• Seminar on recent Electrophysiological
Methods for Evaluation of Neurotoxicity

Intramural Programs and Activities

NIEHS scientists from various intramural
laboratories continue to collaborate with sci-
entists from a number of different nations.
Examples of such collaborative efforts, which
are of mutual benefit and produce information
important to the Institute's research goals, are
listed below:

Comparative Medicine Branch

The Chief of the Comparative Medicine
Branch continues as a charter member of the
International Committee on the Wasting Marmo-
set Syndrome. This condition bears resemblance
to protein-calorie deficiency in man, and the
current focus of attention is on nutrition causa-
tion. Experimental work in the United States and
the Federal Republic of Germany has concen-
trated on diet energy content. Data from 36
participating institutions in six countries were
discussed at a recent meeting held in the United
States.

Laboratory of Biochemical Genetics

The head of the Mammalian Mutagenesis Sec-
tion collaborated with scientists from the Fed-
eral Republic of Germany to exchange informa-
tion on chemicals that induce mutations in
spermatogonia of mice, biochemical screening
for mutants from offspring of treated mice, and
screening for cataract mutations in mice. These
efforts are extremely important to NIEHS in-
ternational efforts in genetic risk assessment
and monitoring of human populations.

Laboratory of Environmental Biophysics

The laboratory continues to collaborate with
scientists from the University of Buenos Aires,
Argentina, on the free-radical metabolism of
gentian violet by Trypanosoma cruzi. As the
agent of Chagas' disease, this microbe infects
millions of people in Argentina and Brazil alone.
Because Trypanosoma cruzi is carried by a
species of the assassin bug found in Texas and
elsewhere in the American South, Chagas' dis-
ease may become established in this country.

The chief of this laboratory participated in an
International Congress on Water and Ions in
Biological Systems, held in Bucharest, Romania,
September 1982. The interdisciplinary nature of
this congress provided a valuable forum for the
exchange of information with a number of dif-
ferent countries.

Laboratory of Environmental Chemistry

Scientists in the Laboratory of Environmental
Chemistry are collaborating with scientists from
the Laboratory of Molecular Biophysics, Oxford
University, England, concerning the X-ray crys-
tallographic properties of cocrystalline states of
dioxin (and related compounds) and selected
proteins. NIEHS scientists are also continuing
their collaboration with the Department of
Pharmacology, University of Urbino, Italy, on
the development of a radio-immunoassay capa-
bility for detecting dioxins applicable to the
Seveso, Italy, dioxin contamination problem; and

with the Canada Center for Inland Waters on the
application of this assay to sediments and fish.
The reliability of this assay as a screening pro-
cedure is being evaluated and has led to the
proposal that this become an American Society
for Testing and Materials standard method.

Laboratory of Pharmacology

The Laboratory of Pharmacology continues its
collaborative research with scientists from the
University of Dundee, Scotland, in which hor-
monal effects on perinatal drug metabolism are
being studied. With scientists from East Ger-
many and Finland, U.S. scientists are also con-
tinuing collaborative efforts on drug metabolism
by isolated skin cells. The laboratory is also
collaborating with colleagues from China on a
project exploring the effects of selenium defi-
ciency on the mitochondrial toxicity of lead.

Laboratory of Pulmonary Function
and Toxicology

Collaborative research efforts are being con-
ducted with colleagues from China on the muta-
genic and carcinogenic properties of nickel salts
and with colleagues from Japan on the role of
chromosome nondisjunction in the carcinogenic
activity of diethylstilbestrol and other car-
cinogens.

Laboratory of Reproductive and
Developmental Toxicology

Collaborative research efforts continued be-
tween the Laboratory of Reproductive and De-
velopmental Toxicology and the University of
Wurzburg, the Federal Republic of Germany, on
the target organ metabolism and bioactivation of
the carcinogen, diethylstilbestrol. Collaborative
efforts with the University of Uppsala, Sweden,
on experimental studies related to the distri-
bution and teratology of 2,3,7,8-tetrachloro-
dibenzadioxin also continued.

Office of the Director

The Associate Director of the Office of
Health Hazard Assessment has remained active
as a member of the International Joint Commis-
sion's Committee on the Assessment of Health
Effects of the Great Lakes Water Quality and is
involved in the evaluation of water pollutant
chemicals and their potential health effects on
the populations in surrounding counties. This
office also participated in an international study
on biological tests in the evaluation of mutagen-
icity and carcinogenicity of air pollutants. The
objective of this study was to examine the rel-
evance of short-term and long-term biological
tests for mutagenicity to the assessment of

human carcinogenic risk that may arise from
exposure to air pollution from motor vehicle
exhausts and coal combustion products.

The Associate Director for Genetics attended
several meetings of the Executive Board and
Commission of the International Commission for
Protection Against Environmental Mutagens and
Carcinogens. These meetings were devoted to
planning ways the commission could develop
mechanisms to foster scientific interchange and
programs in test-method development, valida-
tion, and use in mass-screening programs.

By interagency agreement, the NIEHS con-
tinues to support the Environmental Mutagen
Information Center at the Oak Ridge National
Laboratory. The center works closely with in-
vestigators around the world in both obtaining
and supplying information on environmental
mutagenesis. The center has over 30,000 bibli-
ographic entries in its data banks and remains a
unique worldwide resource for information on
environmental chemical mutagenesis.

The NIEHS has also established the Environ-
mental Teratology Information Center in col-
laboration with the Department of Energy and
Oak Ridge National Laboratory. Information on
teratogenesis is collected, indexed, and made
available to the biomedical community directly
from the center or from the National Library of
Medicine's TOXLINE. The center is a unique
worldwide resource for information on
teratology.

NIH Visiting Program and Health Scientist
Exchange Programs

During FY 1982, collaborative research activ-
ities were carried out in the Institute's intra-
mural laboratories by 68 Visiting Fellows and
Scientists. They came from Argentina, Australia,
Belgium, Canada, China, the German Democra-
tic Republic, the Federal Republic of Germany,
Finland, France, Hungary, India, Israel, Japan,
Korea, Mexico, the Netherlands, New Zealand,
Poland, Sweden, Switzerland, the United King-
dom, Yugoslavia, and Taiwan. Examples of col-
laborative research projects include studies on
the metabolism of the carcinogen 2-acetylami-
nofluorene in rabbit pulmonary and hepatic mi-
crosomes; drug metabolism by isolated lung
cells; mechanisms of hepatic action of nonster-
oidal estrogens; the intracellular binding of lead;
the effects of antioxidants on DNA alkylation;
the mutagenic and carcinogenic properties of
nickel salts; mutagenicity test methods; biome-
try and quantitative risk assessment; neurobe-
havioral, pulmonary, and reproductive toxicity;
and the effects of physical factors on the ner-
vous system.

These research projects were mutually bene- FY 1982, many administrators and scientists

ficial and produced scientific information valu- from all parts of the world visited the NIEHS to

able to the Institute's research goals. Also during be briefed on its programs and activities.

Chapter Xffl
National Eye Institute

Introduction

About ^0 million of the world's people are
blind. The great majority of them are in the
developing nations of Asia, Africa, and Latin
America, but blindness is unnecessarily prevalent
in the industrialized regions of the world as well.
It has been estimated that at least half of all
blindness can be prevented by well-planned sight
conservation programs that use resources and
medical knowledge already available. Mobiliza-
tion of such resources requires a worldwide
effort to increase public and governmental
awareness of the problems of blindness, to pro-
mote the development of effective programs in
countries that now lack them, and to increase
the effective of programs already in existence.
If a cost-effective method were found to slow
down the formation of cataracts so that surgery
could be delayed in the United States by 10 years
alone, for instance, over $500 million per year
could be saved. In much of the developing world
such a new preventive measure could lead to the
elimination of the backlog of millions who are
blind because cataract surgery is not logistically
or economically possible.

The specific objectives of the National Eye
Institute (NEI) international program are these:

• Evaluating available health technologies,
promoting the most cost-effective inter-
vention and prevention programs, and
making these available to affected pop-
ulations;

• Conducting collaborative applied research
studies aimed at developing preventive
methods for dealing with very specific
eye disease; and

• Promoting the controlled clinical evalu-
ation of research findings that appear to
be effective.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

India

Nutritional deficiency is the leading cause of
blindness in children worldwide. In India alone it
is said to account for 180,000 cases. Annually
20,000 children are estimated to become blind
from nutritional deficiencies, primarily vitamin
A, with half of these children surviving and the
other half dying within 1 year. A collaborative
Clinical Research Center for the Prevention of
Nutritional Blindness has been established with
the National Institute of Nutrition in Hyderabad,
India, to attack this problem. The Center will
use U.S. and Indian research bases in an applied
clinical research program. This program will
identify those children who present the highest
risk of becoming blind from hypovitaminosis A
and other concurrent factors, determine prac-
tical ways to prevent this blinding condition, and
develop more cost-effective programs that tar-
get vitamin A prophylaxis to the highest risk
populations. The following collaborative projects
will be carried out at the center:

• Study of the relationship of vitamin A
status in the development of related
keratomalacia and blindness in children;

• Analysis of the role of anterior segment
collagenase activity in the development
of keratomalacia;

• Comparison of the absorption of vitamin
A in diarrhea treated with and without
oral rehydration solution;

• Examination of the relation of vitamin A
status to immunocompetence and infec-
tious morbidity;

• Evaluation of methods for identifying
subclinical vitamin A deficiency in chil-
dren; and

• Determination of risk factors in the
development of xerophthalmia in children.

Final approval of the research agreement
formalizing this collaborative arrangement has
been received from both the Government of
India and the United States, and Center activi-
ties are underway. The NEI has purchased major
laboratory equipment for the Center under a
grant from the U.S. Agency for International
Development. Two Indian scientists have com-
pleted a visit to the United States for training in
special laboratory techniques supportive of the
collaborative projects. Late in the year an NEI
collaborator visited Hyderabad to participate in
the initial activities of the first project. Follow-
up visits by several other NEI collaborators are
anticipated shortly.

NEI scientists and consultants continued their
collaboration with the Indian Government on the
Indian prevention of blindness programs. The NEI
continues to provide consultants in operations
research, biostatistics, and clinical ophthal-
mology.

NEI intramural scientists, Indian scientists and
clinicians from the Aravind Eye Hospital in
Madurai, and engineers from the National Aero-
nautics and Space Administration have been
working for several years to fashion a new in-
strument for removing cataracts more effec-
tively. The scientists and engineers have now
developed and evaluated a technique for removal
of hard cataracts through a small incision with
an air turbine device. The instrument has suc-
cessfully undergone preliminary tests in animals
as well as in vitro with hard cataracts from
Indian patients. In 1982 clinical tests were made
on 30 patients with retinal problems and a poor
prognosis for vision. After the instrument func-
tioned without incident during these tests, it was
turned over to clinicians at the Aravind Eye
Hospital for further clinical development.

3apan

The U.S.- Japan Memorandum of Under-
standing on Vision Research, signed in April
1976, provides for an exchange of scientists
program sponsored by the NEI and the Japan
Society for the Promotion of Science. Two sci-
entists per year from each country may be
selected for the exchange— one short-term (2
weeks to 3 months) and one long-term (3 months
to 1 year). Two Japanese scientists traveled to
the United States under the auspices of this

U.S.-Japan Memorandum of Understanding
during FY 1982.

An assistant professor of anatomy from the
University of Keio, Tokyo, Japan, is spending 1
year, beginning in September 1982, working with
a professor at the Yale University School of
Medicine. They are collaborating on analyses of
synaptogenesis of the retina in fetal monkey
eyes.

Another professor spent 2 months in the
United States, beginning in September 1982,
visiting the NEI's Louisiana State University, and
the University of California at Berkeley to work
on techniques for the correction of certain cor-
neal abnormalities. As a result of this collabo-
ration, the scientists developed a surgical pro-
cedure composed of a photokeratometry system,
epikeratophakia, and thermokeratoplasty to
correct refractive error.

U.S.S.R.

Under the Vision Research section of the
U.S.-U.S.S.R. Program for Health Cooperation,
both sides continued work in the following
problem areas:

• Use of Q-switched laser in the treatment
of glaucoma;

• Assessment of critical flicker fusion to
determine optic nerve function;

• Assessment of gratings to determine optic
nerve function; and

• Clinical studies of ENKAD treatment of
retinitis pigmentosa.

Activities Witli International Agencies

In FY 1982, the NEI continued its activities as
a WHO Collaborating Center for the Prevention
of Blindness, and the Director, NEI, continued to
serve as a member of WHO's Special Advisory
Panel on the Program for the Prevention of
Blindness. This group has been established to
advise WHO in its efforts to eliminate blindness
from the world's population. At the annual
meeting in Geneva, Switzerland, the advisory
group discussed several major topics:

• Program activities, both regional and
global;

• Activities of the WHO Collaborating
Centers for the Prevention of Blindness;

• Low-cost eyeglasses project;

• Strategic approaches to prevent blindness;

100

• Information systems;

• Collaboration with nongovernmental
organizations: current status and future
approaches; and

• Membership of the WHO Program Advi-
sory Group on the Prevention of Blindness.

Over the past year, the Program for the Pre-
vention of Blindness, which is supported pri-
marily by the NEI, has expanded its collection of
data on blindness and its causes. During FY 1982,
for example, several additional surveys of
blindness were developed for Asia and Latin
America.

Extramural Programs

In FY 1983, the NEI made 22 awards to foreign
institutions in eight countries. The research and
training projects supported were representative
of outstanding research projects in all of the
Institute's major research programs: retinal and
choroidal diseases; corneal diseases; cataract;
glaucoma; and strabismus, amblyopia, and visual
processing. Both basic and clinical research
projects were included. Some examples follow:

• To compare various forms of cataract,
scientists at the Oxford (England) Eye
Hospital have been conducting a clinical
trial involving more than 300 patients.
The results of this study, which will be
available in about 3 years, are expected
to define optimal surgical procedures for
cataract extraction and patient optical
rehabilitation. The potential applicability
of these findings is significant because
cataract is a leading cause of blindness
and cataract intervention programs are
conducted worldwide, particularly in
undeveloped countries.

• Glaucoma is another leading cause of
blindness around the world. The reduction
of blindness resulting from the disease,
which depends upon development and
effective distribution of antiglaucoma
drugs, requires a better understanding of
the neuropharmacology of the eye. Two
world-renowned scientists at the Univer-
sity of Uppsala, Sweden, have contributed
significantly to developing basic know-
ledge of the physiology and pharmacology
of the eye. Their findings have led to
development and testing of new drugs for
this devastating eye disease.

• Tens of thousands of infants are born each
year with congenital cataracts. Although
the number and scope of programs for

cataract extraction have been increasing
worldwide, only a small number of chil-
dren with congenital cataracts are
treated early in life. The result is an
irreversible visual deficit for many chil-
dren. To define the critical period in
visual development beyond which irre-
versible vision loss occurs, investigators
at the Hospital for Sick Children in
Toronto, Canada, are evaluating children
who have had congenital cataracts ex-
tracted. Results from these studies will
help define the optimal time for inter-
vention. Such information will help eye
surgeons and health care delivery organ-
izations set priorities among the various
social and economic factors that affect
blindness intervention programs in devel-
oping countries.

International Conferences, Seminars, and Meetings

The Director of the NEI participated in a
course entitled "Community Eye Health" at the
Department of Preventive Ophthalmology, In-
stitute of Ophthalmology, University of London.
At this course he presented a seminar on clinical
trials.

A joint WHO/NEI informal workshop on cata-
ract epidemiology was held at the NEI in June
1982. Most of the participants at this workshop
were representatives of WHO Collaborating
Centers for the Prevention of Blindness. Because
of the rapidly growing impact of cataract, due to
the generally increased life expectancy and
aging of populations in developing countries, the
possible prevention of this disease is gaining
more attention. In this context, epidemiological
studies are of particular importance. To assess
possible risk factors in the formation of cata-
ract, the participants discussed the following
topics:

• Available epidemiological data;

• Identification of risk factors;

• Classification of cataract;

• Biochemical aspects of cataract epide-
miology; and

• Designs for cataract research.

The NEI helped support the WHO Annual
Course on Immunology and Infectious Disease at
Lausanne, Switzerland. This course presents a
unique opportunity to assemble the finest immu-
nologists from the developing world. Before
NEI's participation, ocular immunology had not
been included in the course. In 1982, the course
offered the opportunity for scientists to discuss
various aspects of ocular autoregulation, ocular
immunoregulation, and ocular parasitic disease.
It is hoped that the course will interest re-

101

searchers because onchocerciasis, leprosy, and
toxoplasmosis are major problems in these de-
veloping countries.

The NEI is cooperating with the U.S. Commit-
tee of the International Agency for the Preven-
tion of Blindness in planning its Second General
Assembly. Over 61 countries and 250 individual
participants will gather in Bethesda, Maryland,
October 2k through 28, 1982, for this global
conference, which will be the largest gathering
of experts on blindness prevention ever con-
vened. The theme of the assembly, "New Hori-
zons in Sight," reflects the fact that the lAPB's
original goal—the creation of national commit-
tees throughout the world for the prevention of
blindness—is almost fully achieved and that
many of these committees have been successful
in initiating sight conservation programs in their
countries. At this assembly the results achieved
by many of these programs will be evaluated,
and the most successful ones identified as mod-
els for other countries to follow in the develop-

ment of their programs. It is hoped that by dem-
onstrating the substantial progress achieved to
date, this assembly may convince governments
of developing countries that well-designed
blindness prevention programs should be sup-
ported where they are needed. If this message is
successfully conveyed, the chances are greater
that the battle against preventable blindness
worldwide can be won.

NIH Visiting Program and Health Scientist
Exchange Programs

The NEI continued to serve as an international
center for research and research training in eye
diseases. Thirty-six Visiting Scientists, Fellows,
and other researchers from 17 different coun-
tries around the world participated in research
projects at the NEI campus in Bethesda in FY
1982.

102

Chapter XIV
National Institute of General Medical Sciences

Introduction

The National Institute of General Medical
Sciences (NIGMS) gives financial support for
research and research training to a number of
basic biomedical science disciplines that under-
gird the disease-specific initiatives of the cate-
gorical NIH Institutes.

Extramural Programs

The NIGMS accepts designated grant appli-
cations, which fall within its mission to support
basic biomedical research, from principal in-
vestigators at appropriate institutions in coun-
tries other than the United States; and it funds
those with the highest scientific merit. Eight
such grants were funded during FY 1982 to
principal investigators in four countries: Argen-

tina, Canada, Israel, and the United Kingdom.

The foreign grants were funded by four In-
stitute programs, namely, the Cellular and Mo-
lecular Basis of Diseases Program, the Genetics
Program, the Pharmacological Sciences Pro-
gram, and the Physiology and Biomedical Engi-
neering Program.

International Conferences, Seminars, and Meetings

The NIGMS joined other Institutes at the NIH
to provide foreign travel funds for American and
foreign scientists to participate in two inter-
national conferences: the Twelfth International
Congress of Biochemistry, held in August 1 982 at
Perth, Australia; and the International Confer-
ence on Streptococcal Genetics, held in Novem-
ber 1981 at Sarasota, Florida.

103

Chapter XV
National Institute of Neurological
and Communicative Disorders and Stroke

The National Institute of Neurological and
Communicative Disorders and Stroke (NINCDS)
serves as the unit of the NIH responsible for
basic and clinical research on disorders of the
nervous system and of human communication.
Through its research grant program, application
of P.L. ^80, which permits use of U.S.-owned
foreign currencies in specific countries and
collaborative research projects engaging the
NINCDS scientists and their foreign colleagues,
the Institute maintains a continuing interaction
with international neuroscientists. Because
neurological and communicative disorders are
major problems in virtually every country of the
world, all nations stand to benefit from inter-
national research efforts and interchange of
knowledge. Further, some of the neurological
disorders vary in incidence and severity from
country to country. The study of these variations
and identification of their causes should lead to
a clearer understanding of the causes of the
disorders themselves. Therefore, the potential
impact of international neuroscience research is
great.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

In FY 1982, the NINCDS had a number of
informal agreements in effect. In addition, the
Institute began negotiations with the Govern-
ment of Italy for epidemiological studies of
stroke and the dementias.

In 1982, the NINCDS sponsored four P.L.-^80
projects. Two of these projects were in Poland,
and two were in Egypt. Both Polish projects
concerned neuromuscular disorders, one being a
study of the role of neurological cells in the
processes of myelination and demyelination, and
the other a study of the degree of muscle lesion
in different disease conditions, as well as the
connection between endocrine and muscle dis-
turbances. The Polish groups, located at the

Medical Academy of Warsaw and at the Medical
Academy in Poznan, have access to virtually all
cases of neuromuscular disease in Poland and are
a valuable international research resource.

The two remaining P.L.-^80 projects were
both in Egypt. One concerned perinatal screening
of developmental malformations; the other was a
study of the venoms of poisonous snakes. The
perinatal screening project, in which over
100,000 patients in Cairo and Mansura have now
been studied, has revealed a higher than ex-
pected incidence of spina bifida and anenceph-
aly. Data from this project are undergoing a
comprehensive analysis to discover the reasons
for the higher incidence. The snake venom study,
involving collection of venoms from North and
East Africa as well as from Egypt, has resulted
in publication of six scientific papers in journals
outside Egypt and has put the Government of
Egypt in a position to manufacture good anti-
venins for North and Central Africa.

Activities With International Agencies

Since 1975, the NINCDS has been one of 13
WHO Collaborating Centers in the Neurosci-
ences. These centers, positioned strategically
throughout the world, further international re-
search efforts on neurological disorders and
initiate and demonstrate community programs
for prevention and treatment of these disorders.
Special emphasis is being given to the cerebro-
vascular disorders (stroke), the convulsive dis-
orders (epilepsy), and the neurological and com-
municative disorders related to nutritional and
developmental problems of children. The other
12 Collaborating Centers in the Neurosciences
are:

• The Laboratoires d'Etudes et de Recher-
ches Synthelabo, Paris, France

• The Arthur Vining Davis Center for Be-
havioral Neurobiology, The Salk Institute,
San Diego, California

• The Montreal Neurological Institute,
Montreal, Canada

10^

• The Groupe Hospitaller de la Timone,
Marseilles, France

• The Fundacion Institute Neurologico de
Colombia, Bogota, Colombia

• The Clinique Neurologique, Dakar, Senegal

• The University of Ibadan, Ibadan, Nigeria

• The Institute of Neurology, The Academy
of Medical Sciences of the U.S.S.R., Mos-
cow, U.S.S.R.

• The Centre Medical Universitaire, Ge-
neva, Switzerland

• The Institute Nacional de Neurologia y
Neurocirugia, Mexico City, Mexico

• The Shanghai First Medical College,
Shanghai, China

• The Beijing Neurosurgical Institute,
Beijing, China

Each center funds its own activities and in-
cludes collaborative research, publications for
scientific information exchange, support of
conferences and courses, advisory services,
technical assistance, and training of new inves-
tigators.

As part of this effort, the NINCDS, the NIH
Fogarty International Center, and WHO jointly
sponsor an International Neurosciences Fellow-
ship Program. This program provides men and
women from developing countries with stipends
for advanced training in the United States so
that they can assume leadership roles in aca-
demic and public health careers in the neuro-
sciences in their own countries. In 1982, the
NINCDS supported five international neurosci-
ence fellows from China, four at the NIH and
one at the University of Minnesota Medical
School.

The NIH Visiting Program

During FY 1982, the NINCDS intramural pro-
gram was host to 85 Visiting Scientists, Visiting
Associates, and Visiting Fellows from 58 coun-
tries. Represented were Argentina, Australia,
Austria, Bangladesh, Belgium, Bolivia, Brazil,
Canada, Chile, China, Colombia, Czechoslovak-
ia, Denmark, Egypt, Finland, France, the Federal
Republic of Germany, Ghana, Greece, Guate-
mala, Guyana, Hong Kong, Hungary, India, Iran,
Ireland, Israel, Italy, Jamaica, 3apan, Korea,
Luxembourg, Mexico, Nepal, the Netherlands,
New Zealand, Nigeria, Norway, Pakistan, Pan-
ama, Peru, the Philippines, Poland, Portugal,

Sierra Leone, South Africa, Spain, Sri Lanka,
Sweden, Switzerland, Turkey, the U.S.S.R., the
United Kingdom, Uruguay, Venezuela, Yugo-
slavia, Zimbabwe, and Taiwan.

The contributions of these investigators add
immeasurably to the strength and effectiveness
of the NINCDS Intramural Program, and the
experience and new knowledge they take back
with them to their home countries strengthen
the neurosciences around the world.

Extramural Programs

NINCDS awarded 21 foreign research grants in
FY 1982 to institutions in Canada, Israel, Italy,
Mexico, New Zealand, Sweden, and the United
Kingdom. These grants supported both clinical
and basic research and have been awarded to
outstanding investigators exploring problems of
high priority in the United States and in their
own countries.

the University of Western Ontario received
the largest NINCDS foreign grant in 1982 for the
gathering and analysis of data from approxi-
mately 60 U.S. and foreign medical centers on
the effectiveness of a surgical procedure for
preventing strokes. The procedure—known as the
extracranial/intracranial bypass—involves graft-
ing a scalp artery to an intracranial artery to
improve blood supply. Although the technique is
widely practiced, it is not statistically proven to
be better than other forms of treatment. By
1983 the results of this study will be available to
neurosurgeons and stroke specialists in cill
countries.

International Conferences, Seminars, and Meetings

In 1981, the Institute provided some support
for the World Federation of Neurology Meetings
in Tokyo, 3apan. Several staff members attend-
ed. In 1982, the First International Brain Re-
search Organization World Congress on the Brain
in Health and Disease was held in Lausanne,
Switzerland. The NINCDS provided support for
planning this meeting. In addition, the XII Sym-
posium Neuroradiologicum— held in Washington,
D.C., in 1982— was partially supported by an
NINCDS grant and attracted visitors from many
countries.

Intramural Programs and Activities

Work continues on development of new anti-
convulsant drugs, combining the efforts of
pharmaceutical firms in Europe and Japan. Two
promising drugs, one from Japan and one from
France, are now being tested under NINCDS
contracts. The NINCDS Epilepsy Branch con-

105

tinues to work with Epilepsy International to
innprove the use of anti-epileptic drugs. A team
from the NINCDS Epilepsy Branch is working
with the WHO Neurosciences Collaborating
Center in Mexico to evaluate a protocol for
studying the pharmacokinetics of anticonvulsant
drugs in non-Caucasian populations, particularly
in developing countries.

The NINCDS Laboratory of Central Nervous
System Studies continues research on the slow,
latent, virus-induced brain disorders such as

Creutzfeldt- Jakob disease and on Korean
hemorrhagic disease with renal syndrome. In
reference to the latter, scientists have demon-
strated the presence of the causative agent in
North American rodents.

A continual interchange occurs among
NINCDS intramural and foreign scientists on
topics of interest, not only through scientific
meetings but also through visits to laboratories
and consultations with scientists doing related
work.

106

Chapter XVI
Warren G. Magnuson Clinical Center

Introduction

The Warren G. Magnuson Clinical Center (CC)
was authorized by Congress to provide the high-
quality patient care necessary to conduct bio-
medical research. The 5^6-bed hospital has fa-
cilities and support services for nearly 1,000
physicians who conduct clinical research for 8 of
the 11 NIH Institutes and for the National In-
stitute of Mental Health. Since its establishment
nearly 30 years ago, the CC has served as a
prototype for many research hospitals. It was
specially designed to place patient care facilities
close to research laboratories to promote quick
transfer of new findings of basic and clinical
scientists to the treatment of patients. More
than 'f,000 patients are admitted annually (upon
referral by their personal physicians); and in
accordance with increasing emphasis on pre-
vention and ambulatory health care, outpatients
are now observed and treated at a newly opened
ambulatory care research facility.

The CC ensures the highest possible level of
medical care to each patient; provides optimal
resources and facilities for clinical research;
performs research on methods and systems in-
volved in patient care and study; disseminates
information to professionals and to the public
relevant to clinical investigation; develops and
maintains training programs in the techniques
and ethics of biomedical and clinical research;
and interacts with scientists and physicians,
nationally and internationally, on such mutual
problems of clinical research as policy, educa-
tion, ethics, and priorities.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

A French-American-British (FAB) Coop-
erative Group is developing a uniform classi-
fication of acute leukemias and myeloprolifer-
ative syndromes that will be useful in the prog-
nosis and treatment of patients with these dis-
eases. The group is composed of seven bone

marrow morphologists: two from the United
Kingdom, three from France, and two from the
United States. The Chief of the CC Hemotology
Service is one of the U.S. representatives.

NIH Visiting Program and Health Scientist
Exchange Programs

A Japanese expert consultant has begun a
2-year project to purify the NANB virus (des-
cribed above) and to develop a NANB test sys-
tem. This area is crucial to further clinical
studies of this agent.

Development of assays to detect different
agents for hepatitis and additional epidemiologic
information should decrease the risk of hepatitis
following blood transfusion and permit selection
of low-risk blood donors for safer blood products.

The Clinical Center Blood Bank has been in-
volved in several international collaborative
research projects in the hepatitis area in FY
1982. The primary goals have been evaluation of
data concerning posttransfusion hepatitis in
different populations, collaborative efforts to
identify markers for posttruansfusion hepatitis,
and exchange of scientific informaton and ex-
perience about posttransfusion hepatitis, a dis-
ease that has a significant worldwide distribution.

The risk oif transmitting hepetitis through
blood is affected by a variety of factors—social,
economic, and ethinic. A cooperative sutdy was
undertaken to compare the fequency of hepatitis
viral antigens and anitbodies among blood donors
in the U.S.S.R. and the United States. The re-
sults permit calculation of age and sex preval-
ence of hepatitis B and hepatitis A serologic
markers for blood donors within and between
each country, as well as comparison, on the same
sera, of test methodologies in use in both
countries.

No accepted assay is available for the agent
that transmits non-A, non-B (NANB) hepatitis. A
coded panel of NANB infectious sera and ap-
propriate controls was distributed to investi-
gators in the United Kingdom, France, the Fed-
eral Republic of Germany, and Costa Rica. Blood
Bank investigators have been responsible for the
collation and interpretation of results that have
identified a candidate assay.

107

Chapter XVH
Division of Computer Research and Technology

Introduction

Established in 196'^, the Division of Computer
Research and Technology (DCRT) was designed
to make computational methods a tool for the
NIH biomedical community. Over the years, the
work of the Division has become an integral part
of the conduct and management of NIH research
programs. At the same time, the DCRT has
grown to become the largest biomedical com-
puting facility in the world. DCRT staff mem-
bers continue to create still more powerful and
useful systems. They continually seek new ways
to bring computers, mathematics, and engi-
neering into the service of science and to en-
hance administrative effectiveness.

Summary of International Programs
and Activities

Activities With International Agencies

In a study sponsored by WHO, the Data Man-
agement Branch collaborated with a researcher
from Nigeria in creating a data base for exam-
ining the prevalence of major neurological dis-
eases in that country.

Extramural Programs

DCRT staff members collaborated with sci-
entists from foreign countries including Aus-
tralia, Canada, China, France, Ghana, Green-
land, 3apan, Nigeria, and Singapore. Examples of
these international collaborative activities
include:

• Computer support for flow microfluoro-
metry /cell sorters (Europe and Australia)

• Statistical research in clinical pathology
(Belgium and Japan)

• Multivariate statistical analysis (Australia)

• Theory and measurement of intermolec-
ular forces (Canada)

• Analysis of coupled transport and bio-
chemical kinetics (France)

• Prevalance of major neurological diseases
(Nigeria)

Other visitors to the DCRT throughout the
year included foreign scientists from China, the
Federal Republic of Germany, and the Republic
of South Africa.

International Conferences, Seminars, and Meetings

The Division cosponsored, with the European
Society of Cardiology and others, the annual
conference on Computers in Cardiology. At this
forum physicians, engineers, and computer sci-
entists exchange information on the design of
computer systems and their application to
cardiology.

A delegation of foreign scientists attending
the Sixth Annual Conference on Computers in
Chemistry and Education came to visit DCRT
for a briefing on the varied work of the Division.
Countries represented by this group included
Austria, Belgium, Canada, China, the Federal
Republic of Germany, Finland, France., Hungary,
Israel, Japan, Sudan, Switzerland, the United
Kingdom, and the U.S.S.R.

Intramural Programs and Activities

The Data Management Branch is designing a
system for the computerization of data on bio-
medical scientists and institutions in China.
Officials at the FIC will use the system to brief
NIH and non-NIH scientists interested in bio-
medical research in that country.

The Branch also designed a system that allows
the FIC to maintain and query a data base that
contains information on foreign scientists who
are in the United States to perform health
research.

108

An FIC Fellow in the Laboratory of Applied applied successfully to patients under intensive
Studies of the DCRT has contributed to the care following myocardial infarction,
theory of dynamic risk assessment in acute dis-
ease by creating very general, yet practical, nuj Visiting Program and Health Scientist
methods for sequential analysis of time-depend-
ent multivariant measurement vectors obtained Exchange Programs
during the course of a patient's illness. Combin-
ing these methods with discriminant function Three foreign scientists, two from Israel and
techniques enables daily reassessment of prob- one from Belgium, continued to work at the
able patient outcome. The procedures have been Division during FY 1982.

109

Chapter XVm
Division of Research Resources

Introduction

The Division of Research Resources (DRR)
develops and supports a variety of multicate-
gorical, interdisciplinary research resources
essential to biomedical research. These re-
sources are used by a broad spectrum of inves-
tigators to enhance their own effectiveness and
that of their institutions in responding to and
carrying out the mission of the National Insti-
tutes of Health. The DRR comprises five major
programs: (1) General Clinical Research Centers,
(2) Biotechnology Resources, (3) Minority Bio-
medical Research Support, (4) Biomedical Re-
search Support, and (5) Animal Resources.

Of these, the Animal Resources Program
(ARP) is the most involved in international ac-
tivity. The ARP provides researchers with ani-
mals that are essential for studies on human
disease processes and physiological systems. The
ARP is also concerned with the study and pres-
ervation of animal populations in their natural
environments. The ARP consists of two subpro-
grams: the Primate Research Centers Program
(PRCP) and the Laboratory Animal Sciences
Program (LASP). The PRCP supports seven re-
gional primate research centers and the LASP
supports specialized animal models and colonies,
as well as a variety of other animal resource
projects. Several of these projects are conducted
outside the United States.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

Of increasing international concern is the
preservation of declining nonhuman resources to
support biomedical research at a time of ex-
panding agricultural and industrial development.
To address this issue, the IXth Congress of the
International Primatological Society was held
August 8-13, 1982, in Atlanta, Georgia. It was
hosted by the Yerkes Regional Primate Research
Center and attended by over 700 scientists and
other individuals interested in primatology re-
search, including about 30 representatives from

10 countries that are original habitats for vari-
ous species of nonhuman primates. Overall, the
congress was considered highly successful and a
number of publications related to primate con-
servation will result.

Extramural Programs

The Yerkes Primate Center, a grantee of the
PRCP, provides support to the Kenyan Primate
Center, Kenya, East Africa, for establishment of
a base of information on African primate species
(particularly the baboon in its native habitat);
for exchange of information on these animals;
and for research projects related to the survival
of these animals in their native habitat.

The PRCP provides support through the Wash-
ington Regional Primate Research Center for
Indonesian primate research activities at the
Kutai Field Station. The orangutan, gibbon, and
other primates native to this part of the world
are endangered or threatened species whose
habitats are rapidly being destroyed by industrial
and agricultural development in Indonesia. This
support is important for the development of
information related to the survival of these
species and the continued availability of these
important species for use in biomedical research.

The LASP supports a project in northern India
that focuses on population studies of nonhuman
primates. This project, initiated in 1959 and
supported by ARP since 1973,has provided data
regarding population dynamics and demographic
and reproductive parameters of a natural rhesus
monkey population. One study group has in-
creased 16.8 percent in numbers in the 't years
since the export ban on rhesus monkeys, com-
pared with an increase of 16.5 percent in the ^
years prior to the ban. Since populations with
good birth rates and low infant mortality rates
can increase at the rate of 16 percent per year,
the rhesus population could have been expected
to increase at least 50 percent since the ban.
The actual figures indicate that similar factors
influenced the population both before and after
the ban and that export per se has not been a
dominant factor. Ongoing studies will provide
data on the effects of habitat displacement,
which is occurring with one study group, and the
feasibility of intentional transplants and relo-

110

cation of breeding groups. Such information is
necessary as a guide to conservation and man-
agement of rhesus monkeys and will be impor-
tant in evaluating the potential supply of rhesus
monkeys for biomedical research.

A second project supported by the LASP in-
volves the study of important habitat features of
West African rain forest primates. This project
includes a detailed examination of the relation-
ships between feeding behavior, specific eco-
logical conditions, and social organization. It is

essentially a predictive study in which important
variables such as foraging styles, diet selection,
home range, group size patterns, population
density, distribution, and social interaction are
expected to relate in specific ways to ecological
conditions. The information will be useful, not
only to behaviorists, socio-ecologists, and bot-
anists, but also to conservationists and those
making decisions about the size of forest areas
in Africa necessary to maintain wild populations
of primates.

Chapter XIX
Division of Research Services

Introduction

Through collaboration and cooperation with
national and international organizations, the
Division of Research Services (DRS) plans and
conducts centralized programs of scientific,
engineering, and technical services in support of
biomedical research activities. Professional and
technical staff members consult with research
scientists during all stages of a research project
on the development and use of essential products
and services. DRS personnel provide specialized
assistance and services in biomedical engineering
and instrumentation design and development;
research animal production, maintenance, pro-
curement, and animal disease identification and
control; provide biomedical library and trans-
lation services; and make available specialists in
medical arts and photography.

The DRS is involved internationally in such
activities as developing a primate supply pro-
gram for biomedical research; establishing
training programs in conservation and manage-
ment of wild primates; supplying organizations
and institutions throughout the world with ge-
netically defined rodents as nuclei for colony
development; sponsoring the development of
methods for primate population studies and
surveys; developing programs to train techni-
cians in scientific instruments and to establish
repair and maintenance centers in six univer-
sities in Egypt; and developing a regional pro-
gram for repair and maintenance of hospital
clinical care equipment in the eastern Caribbean
countries of Barbados, St. Lucia, St. Vincent,
Montserrat, St. Kitts, Antigua, and Dominica.

The DRS has detailed to the Department of
State a senior staff member, who has been as-
signed to the U.S. Embassy in New Delhi, India,
as the U.S. Scientific Attache and International
Health Representative. In this assignment he
assists the Scientific Counselor in all matters
relating to U.S. scientific affairs in India with
specific responsibility for representing, moni-
toring, and coordinating the program interests of
the U.S. Department of Health and Human Ser-
vices and other U.S. agencies engaged in health
and health-related activities.

Summary of International Programs
and Activities

Bilateral Agreements and Other
Country-to-Country Activities

Agreement with 3apan on Cooperation in
Research and Development in Science
and Technology

In April 1980, a collaborative project in lab-
oratory animal science was instituted as part of
the U.S. -Japan Non-Energy Cooperative Agree-
ment. The purpose of the project is to promote
the exchange of information on laboratory ani-
mal models, the development and use of uniform
international standards for research animals, and
the exchange of information on other aspects of
laboratory animal science. The DRS has respon-
sibility for U.S. involvement in this project.

Initially, the purpose of the project was to
develop information on quality control of lab-
oratory animals. Several workshops on quality
control provided material to be used in a series
of U.S./3apan laboratory animal quality control
manuals. In addition, representatives from both
countries have actively participated in work-
shops on genetic and microbiological monitoring.

Egyptian Ministry of Health

On April 17, 1980, an agreement was signed
between the Egyptian Ministry of Health and
DHHS. Under a Special Foreign Currency Proj-
ect, the Egyptian Ministry of Health, in coopera-
tion with the Biomedical Engineering and In-
strumentation Branch, National Institutes of
Health, DHHS, will develop a pilot repair and
maintenance center for medical equipment. This
center will service a cross-section of Ministry of
Health medical facilities in Giza. It is antici-
pated that the center, after suitable modifica-
tions, will serve as a model for a program in the
repair and maintenance of medical equipment
applicable nationwide in Egypt.

During 1980, the American Project Officer
and the Egyptian Principal Investigator met to

112

develop an operating plan for the center and an
implementation plan for the project. Project
implementation began in 1981 with the training
of center personnel— both in Egypt and the
NIH--the purchase of equipment supplies for the
center, and the construction of a building to
house the center on the grounds of Hamwandia
Hospital. The center became operational in 1982.

By the end of FY 1982, the center had devel-
oped repair capacity in excess of that required
to service Hamwandia Hospital alone; therefore,
consideration is being given to increasing the
number of hospitals and clinics serviced by the
center.

Under an interagency agreement with the
National Science Foundation, the Biomedical
Engineering and Instrumentation Branch, DRS,
assisted five Egyptian universities in the devel-
opment of repair and maintenance centers for
scientific equipment. This project was carried
out under an agreement between the USAID and
the Egyptian Academy of Scientific Research
and Technology providing for assistance "to help
organize and direct the Egyptian scientific com-
munity toward dealing with the practical prob-
lems inhibiting economic development and social
improvement."

Caribbean

Under a Participating Agency Service Agree-
ment with USAID, the Biomedical Engineering
and Instrumentation Branch is (1) participating in
a joint effort with Project Hope to improve the
repair and maintenance capability of the Jamai-
can Ministry of Health biomedical equipment
repair facilities and develop a biomedical equip-
ment maintenance program at the College of
Arts, Science and Technology in Kingston and (2)
developing a cooperative regional program for
the maintenance hospital clinical care equipment
for the islands of the eastern Caribbean. The
program in the eastern Caribbean will be tai-
lored to meet the individual needs of the coun-
tries involved and will make full use of existing
repair capability, both in the private and in the
public sectors. The implementation plan calls for
the development of two repair centers within the
region to provide repair services throughout the
region. To date, this branch has made site visits
to the countries involved to determine their
repair and maintenance needs, purchased an
inventory of basic maintenance tools and equip-
ment for each of the islands, reviewed the cap-
ability of existing repair and maintenence per-
sonnel in the region, and selected personnel for
training in instrument maintenence.

Activities with International Agencies

World Health Organization: Resource of
Laboratory Rodents

The NIH genetic resource of laboratory ro-
dents has been designated as a collaborating
center for defined laboratory animals by WHO,
and as an international nude mouse reference
center by the International Council on Labora-
tory Animal Science. The resource maintains
over 200 stocks and strains of genetically de-
fined and monitored rodents and rabbits and
serves as a source of breeding nuclei of animals
used by NIH research investigators as well as by
the international biomedical research communi-
ty. Approximately 6,000 animals were supplied
to domestic and foreign research institutions in
FY 1982.

World Health Organization: Primate Supply
Program

A contract has been established with WHO to
develop an international primate supply program.
WHO is to provide expert consultation and ad-
visory assistance to the governments of coun-
tries interested in taking measures to ensure the
continuing availability of nonhuman primates for
use in biomedical research. This contract is
intended to implement recommendations made
by the Interagency Primate Steering Committee
as outlined in the National Primate Plan.

The NIH has a critical interest in the contin-
uing supply of nonhuman primates. Intramural
research programs at the NIH use more non-
human primates than any other government
organization. In addition, NIH extramural re-
search requires one-third of the total animals
used for health-related programs. Another major
user group is the pharmaceutical/biological
industry, where nonhuman primates are required
for the production and testing of drugs and bio-
logic products that are licensed and controlled
by the FDA. Because primate populations are
rapidly declining, and because these animals are
important to human, health-related needs, the
objectives served by the WHO contract are of
the utmost importance.

Pan American Health Organization

The Interagency Primate Steering Committee,
through a contract with PAHO has developed
projects to establish New World primate breed-
ing centers and conservation programs in Latin

113

American countries. Although the majority of
these countries imposed restrictions on the com-
mercial export of nonhuman primates in 1973,
they are interested in providing those species
required for biomedical research through captive
breeding and controlled wildlife management
programs.

Specific objectives of the contract are:

• To provide expert consultants and advice
to Latin American governments inter-
ested in developing primate programs as
recommended by WHO;

• To assist in developing national programs
of wild primate conservation and man-
agement to ensure the perpetuation of
natural nonhuman primate resources; and

• To support development of primate
breeding stations to produce species im-
portant to biomedial research under cap-
tive or semicaptive conditions.

The fully established Peruvian National Pri-
mate Project includes a breeding station in
Iquitos, as well as field management activities.
Marmosets and squirrel monkeys have been pro-
vided from this operation for use in U.S. biomed-
ical activities since 1976.

An agreement was also established between
PAHO and the Government of Colombia to de-
velop a captive owl monkey breeding station at

Armero and to assist in ongoing conservation
programs. Primate breeding and conservation
programs have also been initiated in Brazil.
These programs will eventually become self-
supporting through funds received for primates
made available for scientific use.

In addition to contract support, DRS staff
provided consultive services in FY 1982 to sev-
eral South American countries on matters re-
lated to primate conservation, breeding, and
nutrition. These services are part of the overall
cooperative effort to ensure the availability of
nonhuman primate species as animal models for
human disease.

NIH Visiting Program and Health Scientist
Exchange Programs

A Visiting Scientist from England was re-
cruited to establish an NIH program in zeugma-
tography, a technique for medical diagnostic
imagery based on the principles of nuclear mag-
netic resonance (NMR). Since his arrival in No-
vember 1977, he has conceived and designed an
entirely new method for producing three-
dimensional NMR images. Moreover, he has
successfully tested several major components of
the system, and its first images are expected
within the next few months. In addition, since his
arrival, he has made numerous significant con-
tributions to the scientific literature of NMR
imaging.

llt^

Appendix
Definitions of NIH International Program Activities

Research Awards

Foreign Research Grants

The NIH supports research projects outside the
United States only when they have met special
criteria established for foreign grants. These
criteria include the highest scientific merit and
relevance to the program interests of the NIH as
well as conformance with NIH, DHHS, and other
U.S. policies.

Cooperative Agreement Awards

Cooperative agreement awards are
noncompeting research grants to support
collaborative projects between sponsoring
Institutes and principal investigators, usually
conducted under a formal protocol.

Core Grant to Gorgas Memorial Institute

A core grant to the Gorgas Memorial
Institute/Gorgas Memorial Laboratory in Panama
is appropriated through the budget of the FlC,
NIH. The GML conducts research in tropical
diseases of importance to Central America and
the United States.

Domestic Grants With Foreign Components

A domestic grant with a foreign component is
an NIH-financed grant with a domestic
investigator in which a part of the grant is used
to support research in a foreign country.

International Collaboration in Infectious Diseases
Research Awards

Under the International Collaboration in
Infectious Diseases Research Program, emphasis
is given to developing relationships between U.S.
institutions and counterpart institutions abroad
in infectious diseases research. The ICIDR
Program was begun in 1979 when the Inter-

national Centers for Medical Research, which
had existed from 1962, were phased out. In table
A-1, the data for ICJDR awards are reported
with other "Domestic Grants With Foreign Com-
ponents." In tables A-2 and A-3, ICIDR awards
are reported separately.

International Scientific Meetings

The NIH assists in the support of scientific
meetings held to coordinate, exchange, and
disseminate information when such activities are
directed toward objectives clearly within the
areas of NIH program interests. Activities
reported include international components of
those meetings supported under this research
program area.

Special Foreign Currency (P.L. 480) Grants

The Special Foreign Currency Program,
administered by the FIC, enables the NIH to
support overseas activities that contribute to the
advancement of health sciences in the United
States. Funded by U.S. -owned local excess
currency primarily derived from the sale of
surplus U.S. agricultural commodities, these
activities include biomedical research and the
translation and dissemination of scientific
literature. Funds for the Special Foreign
Currency Program are appropriated to the
Office of the Assistant Secretary for Health,
DHHS, and awarded and administered by the NIH.

Foreign Contracts

Research contracts with institutions outside
the United States must comply with the criteria
prescribed for foreign grants.

Domestic Contracts With Foreign Components

A domestic contract with a foreign component
is an NIH-financed contract with a domestic
institution in which a part of the contract is used
to support research in a foreign country.

115

Scientist Exchanges

Visiting Fellows, Associates, Scientists

The NIH Visiting Program offers talented
scientists throughout the world the opportunity
to share the research resources of the NIH.
Through this program, distinguished scientists at
all levels of their careers are invited to the NIH
to receive further research experience and to
conduct research in their biomedical specialties.

International Research Fellowships

The FIC International Research Fellowship
Program provides awards to foreign scientists in
the formative stages of their careers to come to
the United States for up to 2 years of advanced
research training. Fellows are required to return
to their respective home countries at the
termination of their fellowships.

Scholars-in-Residence

The FIC Scholars-in-Residence Program has
been developed to facilitate the work of indi-
vidual scholars and the exchange of ideas among
scholars, distinguished science leaders, and sci-
ence administrators. Scholars-in-Residence are
nominated by NIH scientists and spend up to 10
months in residence at the NIH.

States, or persons who have been lawfully
admitted to the United States for permanent
residence. With acceptable justification, these
fellowships may be taken at foreign institutions.
Fellowships are not awarded for study leading to
the M.D., D.D.S., D.V.M., or other applied
science degree.

Foreign Work/Study Assignments

The Foreign Work/Study Program involves
overseas work assignments developed by NIH
professionals not only to meet their own training
and experience needs, but also to contribute to
the domestic and/or international goals of the
DHHS. Potential assignments are developed
directly with foreign institutions, U.S.
organizations having overseas installations, or
other appropriate organizations that can provide
a foreign work/study experience to fulfill
program objectives.

International Travel

International travel is defined as travel by NIH
personnel, traveling under DHHS travel orders,
to locations outside the United States, including
Canada and Mexico, to attend international
meetings and to participate in multilateral
organization (e.g., WHO, PAHO) activities. This
category also includes travel under bilateral
exchanges.

Senior International Fellowships

The FIC Senior International Fellowship
Program provides opportunities for established
U.S. faculty members, who have demonstrated
productive scholarship and achieved recognized
stature in their profession, to go abroad to
conduct collaborative research and to share their
expertise. It is intended that this award be a
career-enhancing educational experience with
mutual benefits to both home and host
institutions.

National Research Service Awards

Under NIH National Research Service Awards,
predoctoral, postdoctoral, and special
fellowships to promote training for research in
health-related sciences are granted each year to
U.S. citizens, noncitizen nationals of the United

BID Program Support

Bilateral Exchanges

Bilateral exchanges not only contribute to
advancement of biomedical and behavioral
science for the benefit of health in the United
States, but also serve the purposes of (1)
overcoming social or political barriers (e.g.,
China, U.S.S.R.), (2) fostering sharing of
technical resources and expertise (e.g., France,
Israel, Japan), (3) drawing on unique resources or
settings (e.g., India, Nigeria), and (k) furthering
U.S. foreign policy objectives (e.g., Egypt,
Kuwait). NIH participation is geared to scientific
benefits to be derived. Funding, which is
dependent on competition with other program
needs, is derived from regular BID operating
funds.

116

Figure A-1.— NIH international activities, funding by mechanism, FY 1982

(in millions of dollars)

International
Travel
($1.6)

Special Foreign

Currency (P.L. 480)

Grants ($1.4)

FY 1982 Total for International Activities: $62.1*

*lncludes $3.7 of ''Other Funds" — i.e., not appropriated to NIH

117

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Figure A-3.--NIH international research and research training awards, FY 1973-82

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121

Table A-2.--NIH international research and research training awards
by country /area and mechanism,^ FY 1982

(in thousands of dollars)

Total

Research
grants

Cooperative
agreements

ICIDR

SFCP
(P.L. *80)

Research
contracts

Country /area number amount number amount number amount number amount number amount number amount

Argentina

Australia

Austria

Bangladesh

Belgium

Bolivia

Brazil

Canada

Chile

China

Colombia

Denmark

Egypt

Finland

France

Germany, F.R.

Ghana

Greece

Guatemala

Guyana

Hong Kong

Hungary

India

Iran

Ireland

Israel

Italy

Jamaica

Japan

Korea

Lebanon

Luxembourg

Mexico

Nepal

Netherlands

New Zealand

Nigeria

Norway

Pakistan

Panama

Peru

Philippines

Poland

Portugal

Romania

Sierra Leone

South Africa

Spain

Sri Lanka

Sudan

Sweden

21*
1*5

3
18

122

S
38

2
12

7
21*
t*2
21

2
10

121

103

20^

13
1
22
9
8
5
1

3
3
22
2
1
2

23
2
2

1*52

1,731

1*0

357

1*0

1,2^3

7,W9

151

750

t*65

21*7

1,01*1

532

698

637

170

132

3,070

13^

^^,^19

1,575

3,^93

173

1*7

213

21*

t*3i*

182

31*

57
71

t*3\
20
25
21

133

1*51*
18

382
1,773

38
3

3
1

118
1,301

133

^,311 11

\0i*

250

130

2,130
82

28
12

1^5
58

^72

1,053

1*1*7

\t*

1,981

195

31*5

258

52 12

1,283

7 1,262
1 \i*5

3 1*32

t*2

355

1,228

122

Table A-2.~Continued

Visiting

Int'l Research

Guest

Senior Int'l

Nat'l Research

ProRtam
number amount

Fellows

Researchers
number

Fellows

Service
number

Awards

Country/area

number amount

amount

Argentina

194

140

(7)

Austredia

250

153

(11)

Austria

(7)

Bangladesh

(1)

Belgium

129

(6)

Bolivia

Brazil

145

(7)

Canada

485

(16)

134

Chile

117

China

437

118

(22)

Colombia

(1)

Denmark

(5)

Egypt

(2)

Finland

192

(2)

France

354

167

(22)

Germany, F.R.

181

(29)

Ghana

Greece

170

(3)

Guatemala

Guyana

(2)

Hong Kong

(1)

Hungary

132

(2)

India

102

1,623

112

(15)

Iran

Ireland

116

(1)

Israel

785

114

(13)

Italy

1,140

155

(49)

Jamaica

Japan

192

2,827

132

(51)

Korea

134

(5)

Lebanon

Luxembourg

(1)

Mexico

(2)

Nepal

Netherlands

221

(6)

New Zealand

Nigeria

(2)

Norway

(5)

Pakistan

Panama

(1)

Peru

(2)

Philippines

(1)

Poland

327

104

(5)

Portugal

(1)

Romania

Sierra Leone

South Africa

Spain

243

176

(4)

Sri Lanka

(1)

Sudan

Sweden

245

210

(9)

123

Table A-2.— Continued

Total

Research
grants

Cooperative
afireements

ICIDR

SFCP
(P.L. ttSO)

Research
contracts

Country /area number amount number amount number amount number amount number amount number amoun

Switzerland 3i^ 607

Tanzania 2 51

Thailand 2 k70

Turkey 2 k2

United Kingdom [3tt 3,^97

United States U6 3,177

Uruguay 1 24

U.S.S.R.

Venezuela 2 51

Yugoslavia 17 352

Zimbabwe 1 17

Taiwan 10 168

Stateless

Unspecified 9 118

International Organizations

EORTC
lARC
lUAC
PA HO
WHO

Total

428
2,884

609
1,080

752

199

77tt

1 441

141

127
5

1,512 48,113 197 11,411

1
15

215
504

692
1,925

1 50
8 943

1 13

213
2,380

482

1,074

2,384 19 1,424 53 10,608

124

Table A-2.~Continued

Visiting

Int'l Research

Guest

Senior Int'l

Nat'l Research

Program
number amount

Fellows

Researchers
number

Fellows

Service Awards

Country/area

number amount

Switzerland

190

(12)

4 66

Tanzania

Thailand

Turkey

(2)

United Kingdom 70

1,070

(16)

260

21 381

United States

[i^(>

3,177

(9)

Uruguay

(2)

U.S.S.R.

(2)

Venezuela

(f)

Yugoslavia

1^3

(2)

Zimbabwe

Taiwan

114

(2)

Stateless

(1)

Unspecified

9 118

International (

Drganizations

EORTC

«.

_ _

lARC

lUAC

PAHO

WHO

Total

979

15,722

153

3,061

(372)

593

59 985

NOTE: Numbers in parentheses are not added into totals.
Totals may not add due to rounding.

Table A-2 includes only those categories in table 1 that constitute research and research training awards.

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127

Index by Country

Argentina, 19, 25, ^1, ^2, 44, 58, 59, 86, 96, 97,

105
Australia, 2, 7, 14, 19, 20, 25, 41, 58-60, 63-65,

67, 72, 74, 86, 91, 97, 103, 105, 108
Austria, 19, 38, 41, 65, 71, 91, 105, 108
Bangladesh, 62, 65, 74, 84, 86, 105
Belgium, 19, 25, 41, 59, 65, 71, 86, 97, 105,

108, 109
Bolivia, 105
Brazil, 2, 19, 25, 37, 41, 42, 44, 45, 58, 69, 72,

74-76, 84, 86, 91, 96, 105, 114
Canada, 2, 7, 20, 39, 41, 44, 45, 46, 58, 59, 65,

67, 71, 72, 86, 91, 96, 97, 101, 103-105,

108, 116
Chile, 19, 20, 42, 44, 58, 72, 105
China, 3, 4, 6, 7, 11, 14, 15, 19, 20, 25, 26, 29,

35, 36, 43, 45-47, 59, 62, 65, 72, 74, 76,

84-87, 89, 93, 97, 105, 108, 116
Colombia, 6, 41, 42, 44, 67, 74, 84, 86, 105, 114
Denmark, 14, 19, 41, 58, 86, 105
Dominican Republic, 7, 73, 11., 86
Egypt, 2, 4, 20, 22, 24, 25, 29, 35, 36, 41, 43,

47, 67, 68, 72, 74, 11, 86, 93, 104, 105,

112, 113, 116
Finland, 1, 19, 25, 41, 44, 47, 63, 64, 72, 96,

97, 105, 108
France, 7, 14, 18-22, 25, 30, 35-37, 41, 43,

46-48, 59-61, 63-65, 67, 71, 72, 74, 85, 86,

91, 97, 104, 105, 107, 108, 116
Germany, 11, 14, 18, 20, 21, 25, 29, 31, 35, 36,

41, 43, 45, 46, 48, 59, 64, 65, 67, 72, 1%

78, 85, 86, 96, 97, 105, 107, 108
Ghana, 41, 65, 74, 78, 86, 105, 108
Greece, 25, 41, 59, 65, 72, 105
Guyana, 105

Hong Kong, 7, 15, 59, 71, 105
Hungary, 21, 22, 25, 29, 31, 35, 36, 41, 65, 72,

86, 97, 105, 108
Iceland, 41
India, 2, 6, 14, 19, 22-25, 41, 49, 59, 62, 65,

67, 68, 72, 74, 78, 79, 84, 86, 87, 97, 99,

100, 105, 110, 112, 116
Iran, 41, 105
Ireland, 19, 59, 105
Israel, 2, 14, 19, 20, 25, 39, 41, 43, 44, 45, 49,

50, 58, 59, 63-65, 67, 71, 72, 74, 79, 86,

89, 91, 97, 103, 105, 108, 109, 116
Italy, 2, 14, 19, 20, 25, 26, 29, 32, 35, 36, 41,

43, 46, 50, 59, 64, 65, 67, 72, 79, 86,

94-96, 104, 105
Jamaica, 45, 58, 59, 105
Japan, 2, 3, 5-1, 15, 19, 25, 32, 33, 35, 36, 41,

43, 46, 5% 51, 59-62, 65, 67, 72, 74,

78-80, 85, 86, 88, 91, 94, 97, 100, 105,

108, 112, 116
Kenya, 6, 25, 41, 84, 110

Korea, 19, 41, 59, 65, 86, 91, 97, 105

Kuwait, 1, 45, 51, 74, 116

Lebanon, 19, 86

Luxembourg, 105

Mexico, 6, 19, 25, 26, 41, 42, 44, 45, 58, 67,

71, 74, 80, 82, 84, 86, 91, 97, 105, 106, 116
Nepal, 105

Netherlands, 19, 41, 59, 64, 65, 74, 80, 81,

84-86, 96, 97, 105
New Zealand, 7, 19, 41, 59, 65, 72, 91, 97, 105
Nigeria, 1, 6, 19, 25, 41, 51, 65, 74, 81, 84, 86,

88, 90, 105, 108, 116
Norway, 19, 41, 52, 59, 89, 105
Pakistan, 16, 22, 23, 25, 65, 81, 84, 105
Panama, 11, 26, 27, 74, 81, 86, 115
Peru, 6, 19, 41, 42, 44, 105
Philippines, 6, 7, 41, 59, 86, 88, 105
Poland, 3, 18, 19, 22-25, 29, 33, 35, 36, 41, 45,

46, 52, 59, 65, 67, 68, 72, 74, 88, 97, 104,

105
Portugal, 28, 65, 105
P.R.C., 29, 41, 46, 47, 1% 76, 93
Romania, 18, 21, 22, 25, 59, 96
Senegal, 25, 105
Sierra Leone, 74, 81, 86, 105
Singapore, 15, 108

South Africa, 15, 41, 65, 67, 81, 86, 105, 108
Spain, 19, 25, 41, 52, 65, 82, 105
Sri Lanka, 41, 72, 82, 105
Sudan, 19, 74, 82, 108
Sweden, 2, 14-16, 18-20, 41, 52, 59, 63, 65-67,

72, 74, 86, 89, 91, 97, 101, 105
Switzerland, 18-21, 37, 39, 41, 59, 65, 67, 72,

74, 85, 86, 97, 100, 101, 105, 108
Tanzania, 41, 43
Thailand, 41, 58, 62, 74, 76, 84
Turkey, 41, 59, 72, 105
U.S.S.R., 5, 18, 21, 22, 25, 28, 34-36, 41, 43,

45, 46, 53-57, 61, 63, 71, 72, 82, 85, 86,

94, 95, 100, 105, 107, 108, 116
United Kingdom, 2, 19, 20, 41, 59, 62, 64-67,

74, 84, 86, 103, 105, 107, 108, 1-7, 11,

13-15, 19, 21-37, 39, 43, 45-50, 52-59,

62-65, 68, 1% 71
United States, 73, 74, 76, 80, 84, 85, 87-91,

93, 94, 24, 99, 100, 103, 105, 107, 108,

110, 115, 116
Uruguay, 19, 41, 42, 44, 105
Venezuela, 6, 25, 41, 42, 51, 7t^, 86, 105
West Indies, 11, 19
Yugoslavia, 18, 19, 21-23, 25, 41, 58, 64, 65,

67, 72, 88, 97
Zambia, 41

Zimbabwe, 25, 65, 105
Taiwan, 7, 15, 19, 41, 59, 86, 97, 105

128

Index by Research Area

Aged, aging, 1, 7, 24, 52, 53, 58, 64, 70-72, 76,
101

Allergy and infectious diseases
Allergy, 1, 20, 73, 76
Communicable disease, 83
Immunology, 16, 22, 23, 26, 30, 31, 33-35,
37, 40, 56, 71, 74-78, 80, 82-85, 91,
101
Infectious disease, 23, 80, 83, 84, 101

Arthritis and skeletal diseases, 5, 21, 61, 63

Cancer, 1-5, 15, 16, 21, 23, 25, 27-44, 51, 72,
76, 88, 93, 94

Cardiovascular, pulmonary, and blood systems
Anemia, including sickle cell anemia, 5,

17, 59, 61
Blood, 1, 4-6, 13, 15, 17, 19, 24, 27, 31,

45-53, 55-60, 62, 64, 72, 81, 105, 107
Cardiovascular/cardivascular disease, 1,

5-1, 23, 25, 26, 45-53, 55, 57-59
Coronary /coronary disease, 6, 7, 13, 45,

46, 49-52, 54, 55, 57-53
Heart, 1, 5-7, 13, 15, 45-47, 49-59
Hypertension, 6, 7, 13, 23, 45-49, 51, 52,

55-60, 64
Lung, 1, 15, 28, 29, 32, 33, 43, 44, 45-47,

60, 93, 96, 97

Clinical trials, 31-33, 41, 43, 46, 59, 82, 101

Dental/Oral health, 1, 90, 91

Diabetes, 5, 17, 19-21, 59, 61, 63, 64

Endocrinology, 14, 40, 63, 89

Environmental health, including occupational
health, 2, 23, 93-95

Epidemiology, 15, 17, 25, 27, 29-32, 35, 37, 39,
40, 43, 44, 47, 48, 53, 56, 59, 64, 73,
77-79, 81, 82, 85, 88, 89, 101

Eye/vision, including glaucoma, 2, 13, 15, 17,
22, 24, 61, 62, 99-102

Genetics, growth, and reproductive studies
Child health, 7, 23, 87
Family planning, 87

Genetics, 5, 7, 16, 35, 40, 49, 51, 56, 64,
72, 75, 76, 83, 87, 89, 91, 94, 95, 97,
103
Growth, 4, 16, 33, 38, 44, 54, 62, 87, 89, 93
Human development, 7, 71, Z7

Hepatic, renal, and digestive systems
Digestive diseases, 61
Kidney, 5, 19, 31, 61, 63, 64, 68, 72, 82,

106
Liver, 3-5, 29, 32, 34, 44, 65, 97

Information sciences

Information systems, 58, 66, 69, 82, 101
Library, 24, 36, 37, 39, 66-69, 97, 112

Metabolic diseases/metabolism, 30, 32, 50,
53-55, 62-65, 72, 82, 96, 97

Neurological disorders and stroke
Epilepsy, 6, 104-106
Neuroepidemiology, 6
Neurological disorders, 104
Stroke, 2, 6, 13, 50, 51, 59, 60, 104, 105

Nutrition, 15, 29, 44, 45-47, 51, 59-62, 64, 71,
87, 88, 90, 96, 99, 114

Prevention, 1-3, 5, 13, 15, 24, 26, 28, 31-33,
35, 37, 40, 43-47, 49, 51, 52, 54, 58, 64,
73, 77, 78, 87, 90, 93, 99-102, 104

liU.S. GOVERNMENT PRINTING OFFICE: 1983-38 1-132:3154

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